COR LOE Recommendations I C-LD In patients with life-threatening VT or VF associated with confirmed or clinically suspected myocarditis, referral to centers with mechanical hemodynamic support and advanced arrhythmia management is IIb C-LD In patients with giant cell myocarditis with VF or hemodynamically unstable VT treated according to GDMT, an ICD and/or an antiarrhythmic medication may be considered if meaningful survival of greater than 1 year Recommendation-Specific Supportive Text 1. Myocarditis is an inflammatory process often related to infection.S7.5-1,S7.5-5 S7.5-9 When patients are treated in centers with the availability of mechanical hemodynamic support proce- dures, cardiac catheterization, endomyocardial biopsy, advanced cardiac imaging procedures, and arrhythmia management including ICD implantation, outcomes appear improved.S7.5-1 The acute course of myocarditis varies ranging from an asymptomatic finding of transient ST-T changes noted on ECG to cardiogenic shock and recurrent VA.S7.5-10 S7.5-12 Acute management is largely supportive and can rapidly advance to requiring mechanical support.S7.5-13,S7.5-14 Cardiac arrhythmias range from conduction abnormali- ties to life-threatening VT and VF.S7.5-15 S7.5-17 Arrhythmias may require antiarrhythmic medi- cations and/or device therapy.S7.5-18 Giant cell myocarditis is fairly uncommon, but it is of particular importance because it typically affects young individuals and is usually fatal if VT may require antiar- rhythmic medications such as amiodarone and/ or an ICD that in some instances can be used as a bridge to more advanced HF therapies such as LVAD or transplant. Myocarditis and SCD have been reported with HIV infection.S7.5- Systemic lupus erythematous can cause myocarditis but only rarely VT or VF.S7.5-8,S7.5-22 In patients with Chagas disease, acute myocardi- tis is rare but more than one third of affected patients develop late myocardial damage with progressive HF. Conduction defects with pro- gression to complete heart block and VT or VF are common.


Conduction defects with pro- gression to complete heart block and VT or VF are common. Amiodarone appears to be effec- tive in treating VA.S7.5-23 An ICD is frequently used in the late phase of myocarditis,S7.5-24 and radiofrequency catheter ablation has been suc- cessfully used to control recurrent VA in some 2. Giant cell myocarditis is fairly uncommon, but it is of particular importance as it typically affects young individuals and is usually fatal if untreated. The diagnosis is confirmed by endo- myocardial biopsy. Patients may develop heart block, requiring a temporary or a permanent pacemakers. An ICD and antiarrhythmic medica- tions, such as amiodarone are often used in the acute phase to treat VT or VF and reduce the risk 7.6. Cardiac Sarcoidosis Recommendations for Cardiac Sarcoidosis References that support the recommendations are summarized in Online Data Supplement 33.


Cardiac Sarcoidosis Recommendations for Cardiac Sarcoidosis References that support the recommendations are summarized in Online Data Supplement 33. COR LOE Recommendations I B-NR In patients with cardiac sarcoidosis who have sustained VT or are survivors of SCA or have an LVEF of 35% or less, an ICD is recommended, if meaningful survival of greater than 1 year is expected.S7.6-1 S7.6-5 IIa B-NR In patients with cardiac sarcoidosis and LVEF greater than 35% who have syncope and/ or evidence of myocardial scar by cardiac MRI or positron emission tomographic (PET) scan, and/or have an indication for permanent pacing, implantation of an ICD is reasonable, provided that meaningful survival of greater than 1 year is IIa C-LD In patients with cardiac sarcoidosis and LVEF greater than 35%, it is reasonable to perform an electrophysiological study and to implant an ICD, if sustained VA is inducible, provided that meaningful survival of greater than 1 year is expected.S7.6-11,S7.6-12 IIa C-LD In patients with cardiac sarcoidosis who have an indication for permanent pacing, implantation of an ICD can be IIa C-LD In patients with cardiac sarcoidosis with frequent symptomatic VA and evidence of myocardial inflammation, immunosuppression in combination with antiarrhythmic medication therapy can be useful to reduce VA burden.S7.6-14 S7.6-16 CLINICAL STATEMENTS AND GUIDELINES Recommendation-Specific Supportive Text 1. Sarcoidosis is a systemic granulomatous disease of unknown cause. Pulmonary involvement is most frequent but any organ can be affected.


Pulmonary involvement is most frequent but any organ can be affected. Cardiac involvement, diagnosed by cardiac MRI or positron emission tomography (PET), has been reported in up to 55% of patients with extra- cardiac disease, while isolated cardiac sarcoidosis was seen in most patients diagnosed with cardiac Cardiac manifesta- tions include conduction abnormalities, VA, and depressed ventricular function with or without HF, and these contribute greatly to a higher mortality in cardiac sarcoidosis compared with sarcoidosis without cardiac involvement.S7.6-2 In a 25-year study of 110 patients with cardiac sarcoidosis in Finland with HF at presentation, marked LV dysfunction at diagnosis (LVEF <35%), and iso- lated cardiac sarcoidosis predicted an adverse VA can also occur in patients with relatively normal LV function, some of whom have RV involvement that can mimic arrhythmo- genic right ventricular cardiomyopathy. Several reports of patients with cardiac sarcoidosis and ICDs implanted for either primary or secondary prevention of SCD show a high frequency of appropriate ICD therapies,S7.6-3 S7.6-5 supporting use of ICDs for primary and secondary prevention of SCD according to the indications applied for other cardiomyopathies. The frequency of con- duction abnormalities often warrants a device that provides bradycardia pacing as well. 2. Patients with cardiac sarcoidosis can experience VA and SCD, even if the LVEF is normal, and approaches to identification of patients at risk of SCD despite preserved LV function are not well defined. A number of studies have evaluated the role of cardiac MRI for predicting VA and SCD. A which included 760 patients in 10 studies, found that late gadolinium enhance- ment was associated with increased all-cause mortality and more VA compared with those with- out late gadolinium enhancement. Applicability is limited by the lack of precise quantification of late gadolinium enhancement burden that may allow for more nuanced risk stratification.


Applicability is limited by the lack of precise quantification of late gadolinium enhancement burden that may allow for more nuanced risk stratification. Some stud- ies suggested that a threshold effect exists, with extensive LV and RV involvement being a particu- larly high-risk feature.S7.6-7,S7.6-8 However, late gad- olinium enhancement can be present even if the LVEF is >50% and was associated with a risk of death or VT of 4.9% per year compared to 0.24% per year when late gadolinium enhancement was absent in 1 observational study.S7.6-7 PET for assess- ing inflammation and scar is also being increas- ingly used, but data are limited. In 1 report, the Figure 8. prevention of SCD in patients with cardiac sarcoidosis. Colors correspond to Class of Recommendation in Table 1. See Section 7.6 for discussion. *ICD candidacy as determined by functional status, life expectancy, or patient preference. For recurrent sustained monomorphic VT, refer to Figure 2. CEP indicates electrophysiological; GDMT, guideline-directed management and therapy; ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; MRI, magnetic resonance imaging; PET, positron emission tomography; SCA, sudden cardiac arrest; SCD, sudden cardiac death; VA, ventricular arrhythmia; and VT, ventricular tachycardia. CLINICAL STATEMENTS AND GUIDELINES presence of inflammation and RV involvement on PET scanning was associated with increased risk of death or e g of relatives.S7.6-10 Electrophysiological studies in a series of 76 patients with evidence of cardiac sarcoid found that 11% had inducible VT. During a median follow-up of 5 years, 75% of patients with inducible VT had spontaneous VT or death compared with 1.5% of those who did not have inducible VT.S7.6-18 3.


CLINICAL STATEMENTS AND GUIDELINES presence of inflammation and RV involvement on PET scanning was associated with increased risk of death or e g of relatives.S7.6-10 Electrophysiological studies in a series of 76 patients with evidence of cardiac sarcoid found that 11% had inducible VT. During a median follow-up of 5 years, 75% of patients with inducible VT had spontaneous VT or death compared with 1.5% of those who did not have inducible VT.S7.6-18 3. Electrophysiological study has been proposed as a potential tool for risk stratification of VA and SCD in patients who had demonstrable evidence of cardiac sarcoidosis based on imaging studies or biopsy, but do not have documented arrhythmias or arrhythmic symptoms nor meet standard pri- mary prevention criteria for ICD implantation. One study evaluated 76 patients with document- ed cardiac sarcoidosis by PET or cardiac MRI who underwent electrophysiological study.S7.6-12 Eight (11%) were inducible for sustained VAs and re- ceived an ICD, while the rest did not receive an ICD because they were not inducible. LVEF was lower in patients with inducible VA (36.4 + 4.2% versus 55.8 + 1.5%). Over a median follow-up of 5 years, 6 of 8 patients in the group with inducible VA had VA or died, compared with 1 death in the negative An important caveat is that it remains unclear if electrophysiological study is more predic- tive than LVEF alone, because inducibility appears to reversely correlate with LVEF. Furthermore, in this study the average LVEF of the inducible patients de- clined further during the followup period.S7.6-12 4. In addition to VA and LV dysfunction, conduction abnormalities, including heart block, can also be a common manifestation of cardiac sarcoidosis. Patients with documented VA and LV dysfunction are at increased risk of cardiac events including cardiac death.


Patients with documented VA and LV dysfunction are at increased risk of cardiac events including cardiac death. One study compared outcomes in 22 patients with high-degree atrioventricular block as the initial manifestation of cardiac sar- coidosis, to 31 patients who initially presented with VT and/or HF. After a median follow up of 34 months, the patients who presented with heart block had fewer HF hospitalization, yet fatal car- diac events, including sustained VAs, were similar to those with VT and/or HF, suggesting that the risk of fatal cardiac events is high regardless of the initial clinical presentation.S7.6-13 In the same study, administration of steroids led to some clini- cal improvement, with some patients recovering conduction, yet steroid effectiveness was not uni- versal and did not seem to be protective against adverse cardiac events.S7.6-13 5. Several studies have attempted to evaluate the role of immunosuppression for reducing VA in patients with cardiac sarcoidosis, but results have been inconsistent.S7.6-14 S7.6-16 Furthermore, a worsening of VA has been reported with immunosuppressive therapy (usually glucocorti- coids) in a number of patients, including electri- cal storm developing in some within 12 months of initiating therapy.S7.6-15 One study reported a decrease of arrhythmia burden with steroid ther- apy but only when given in the early stages of the disease; those with advanced LV dysfunction did not experience benefit.S7.6-16 A systematic combined treatment approach was successful in 63% of patient in a series in which medical ther- apy included both steroids and antiarrhythmic medications, followed by radiofrequency cath- eter ablation if needed.S7.6-14 Immunosuppressive therapy may serve a dual purpose beyond arrhythmia effects as it may help stabilize dis- ease progression and prevent further deteriora- tion of LV function, although this has yet to be demonstrated in RCTs.


Several studies have attempted to evaluate the role of immunosuppression for reducing VA in patients with cardiac sarcoidosis, but results have been inconsistent.S7.6-14 S7.6-16 Furthermore, a worsening of VA has been reported with immunosuppressive therapy (usually glucocorti- coids) in a number of patients, including electri- cal storm developing in some within 12 months of initiating therapy.S7.6-15 One study reported a decrease of arrhythmia burden with steroid ther- apy but only when given in the early stages of the disease; those with advanced LV dysfunction did not experience benefit.S7.6-16 A systematic combined treatment approach was successful in 63% of patient in a series in which medical ther- apy included both steroids and antiarrhythmic medications, followed by radiofrequency cath- eter ablation if needed.S7.6-14 Immunosuppressive therapy may serve a dual purpose beyond arrhythmia effects as it may help stabilize dis- ease progression and prevent further deteriora- tion of LV function, although this has yet to be demonstrated in RCTs. Steroids do not appear to reverse advanced ventricular dysfunction once present, which supports the importance of early diagnosis and intervention.S7.6-1 PET scanning for assessing inflammation and scar is being increas- ingly used in sarcoidosis as well, but data sup- porting its use for guiding therapy of arrhythmias are limited. 7.6.1. Other Infiltrative Cardiomyopathies Infiltrative cardiomyopathies are a heterogeneous group of uncommon systemic diseases with associat- ed cardiac involvement. In some infiltrative cardiomy- opathies, such as Fabry s disease, VAs are uncommon. Some, such as hemochromatosis, are highly treatable especially when diagnosed early. In all cases, treat- ment of the underlying condition must accompany management of cardiac arrhythmias. Most studies of infiltrative cardiomyopathies and arrhythmias are small and observationalS7.6.1-1 but, in general, unless contraindications are present, VAs should be treated as in any other cardiomyopathy. See Section 7.6 for sarcoidosis.


Most studies of infiltrative cardiomyopathies and arrhythmias are small and observationalS7.6.1-1 but, in general, unless contraindications are present, VAs should be treated as in any other cardiomyopathy. See Section 7.6 for sarcoidosis. Until recently, cardiac amyloidosis was associated with a very poor prognosis with patients ultimately succumbing to progressive HF.S7.6.1-2 This perception is changing with advances in medical therapy for light-chain amyloidosis, which have led to improved outcomes.S7.6.1-3 Yet, decisions must be individualized because data remain too limited to al- low formal recommendations as published reports on ICD effectiveness in amyloidosis are small, observa- tional and with limited follow up.S7.6.1-4 Whether there is greater benefit to ICD placement in light chain amyloidosis versus transthyreitin-related amyloidosis remains uncertain, because most studies included mainly patients with amyloid light-chain amyloidosis for which the rate of VA may be greater and prog- CLINICAL STATEMENTS AND GUIDELINES nosis is generally worse. Whether ICDs are effective for primary prevention of SCD is uncertain, but many deaths in patients with cardiac amyloidosis do not ap- pear to be preventable by an ICD.S7.6.1-2 7.7. Heart Failure 7.7.1. HF With Reduced Ejection Fraction Recommendation for HFrEF References that support the recommendation are summarized in Online Data Supplement 35. COR LOE Recommendation IIa B-NR In patients with HFrEF who are awaiting heart transplant and who otherwise would not qualify for an ICD (eg, NYHA class IV and/ or use of inotropes) with a plan to discharge home, an ICD is reasonable.S7.7.1-1 S7.7.1-5 Synopsis Patients with HFrEF are at an increased risk for VA and SCD. The risk is increased irrespective of HFrEF SCD makes up a greater proportion of deaths in patients with milder HF symptoms and lesser proportion in those with moderate/severe HF The reported incidence of SCD varies depending on the definition used and the population studied.


The risk is increased irrespective of HFrEF SCD makes up a greater proportion of deaths in patients with milder HF symptoms and lesser proportion in those with moderate/severe HF The reported incidence of SCD varies depending on the definition used and the population studied. Although many deaths, classified as sudden, are indeed due to lethal VA, others may be due to bradyarrhythmias, pulseless electrical activity, and sud- den hemodynamic deterioration.S7.7.1-7 S7.7.1-9 Medical therapy with neurohormonal agents de- creases the risk of SCD by reducing both the incidence of VA and disease progression.S7.7.1-7,S7.7.1-10 S7.7.1-12 De- spite GDMT for HFrEF, some patients remain at risk for SCD, and an ICD may be helpful. See Sections 7.1 and 7.2 for the indications on ICDs in patients with reduced LVEF. CRT, in appropriate patients, has also been shown to reduce the incidence of SCD.S7.7.1-13 The pathophysiology of SCD in HF is complex, re- sulting from interactions between both functional and structural changes that occur in patients with HFrEF that result in increased susceptibility to SCD.S7.7.1-14 Although many of the risk factors are shared among HFrEF patients, the reason that SCD strikes a particular individual is usually unknown; however, some individu- als may have a genetic susceptibility.S7.7.1-15 Varying de- grees of myocardial fibrosis, neurohormonal activation, and increased wall stress alter the electrophysiological properties with changes in cell coupling, ionic currents (electrical remodeling), and calcium handling that likely contribute to the development of lethal VA.S7.7.1-16 Con- tributing factors extrinsic to the heart include electro- lyte abnormalities related to volume shifts and diuretic use, sympathetic activation, hemodynamic stress, and hypoxia. Recommendation-Specific Supportive Text 1. Many patients with advanced HF listed for heart transplant would not otherwise qualify for ICD given the severity of illness including NYHA class IV status and/or use of inotropic infusion.


Many patients with advanced HF listed for heart transplant would not otherwise qualify for ICD given the severity of illness including NYHA class IV status and/or use of inotropic infusion. Although no randomized data on ICD use in this popula- tion exist, data from observational and large registry studies of patients awaiting heart trans- plant suggest improved survival in patients with One alternative to ICD in this population is the wearable cardioverter- The recommendation in this section is relevant to those patients without an ICD where there is a plan to discharge the patient to home to await cardiac transplant and not, for example, to those patients who remain hospitalized with no intention to discharge home until transplant occurs. For those patients with an LVAD, the decision to place an ICD is gener- ally independent of whether they are awaiting heart transplant but rather the indication in those patients is generally based on the need to treat 7.7.2. HF With Preserved Ejection Fraction Nearly half of the patients with HF have a preserved These patients tend to be older and have more comorbidities than patients with HFrEF. Howev- er, although the rate of SCD is lower in patients with HF with preserved ejection fraction (HFpEF) than in patients with HFrEF,S7.7.2-2 nearly a quarter of all deaths among patients with HFpEF are sudden.S7.7.2-3 S7.7.2-5 The challenge in preventing SCD in patients with HF- pEF is identifying which patients are at a high enough risk to benefit from preventive therapies. Studies ex- ploring noninvasive risk factors for SCD in patients with HFpEF do not identify consistent factors with the exception of ischemic heart disease.S7.7.2-2,S7.7.2-6 Consequently, there is no accepted noninvasive test to identify high-risk patients with HFpEF.


Studies ex- ploring noninvasive risk factors for SCD in patients with HFpEF do not identify consistent factors with the exception of ischemic heart disease.S7.7.2-2,S7.7.2-6 Consequently, there is no accepted noninvasive test to identify high-risk patients with HFpEF. Invasive risk stratification with an electrophysiological study shows promise in this population.S7.7.2-7,S7.7.2-8 This topic is cur- rently being studied in the PRESERVE-EF (Risk Strati- fication in Patients With Preserved Ejection Fraction) trial (NCT02124018). Whether to include a recommendation related to an electrophysiological study in patients with HFpEF and ischemic heart disease was carefully considered by the writing committee. However, evidence was deemed insufficient to support a formal recommendation. Still, the pros and cons of an electrophysiological study can reasonably be considered in select patients with HFpEF and ischemic heart disease who are experiencing symp- toms suggestive of a VA. CLINICAL STATEMENTS AND GUIDELINES 7.7.3. Left Ventricular Assist Device Recommendation for Patients With an LVAD References that support the recommendation are summarized in Online Data Supplement 36. COR LOE Recommendation IIa C-LD In patients with an LVAD and sustained VA, an ICD can be beneficial.S7.7.3-1 Recommendation-Specific Supportive Text 1. Patients with an LVAD have a high risk of VA, particularly those with a history of The increased risk of VA may be due to myocardial irritation from insertion of the LVAD inflow cannula, LV compression due to a suctioning effect from the LVAD, inotropic support frequently needed by some patients, and repolar- ization changes that can occur after LVAD place- ment. Although VT/VF is tolerated by some patients with an LVAD, others experience a decrease in flow as the RV is unsupported; syncope and hypoperfu- sion can result. Having an ICD can allow for prompt termination of VA before significant hemodynamic consequences occur.


Having an ICD can allow for prompt termination of VA before significant hemodynamic consequences occur. Data on ICDs in patients with an LVAD are from observational series. A system- atic review of 6 observational studies observed that within 7 months, 26% of patients with an LVAD The death rate was lower among patients who previously had an ICD (16% versus 32%), suggesting a 39% relative-risk reduction in all-cause mortality in an adjusted analysis.S7.7.3-1 Patients with a history of pre-LVAD VA have nearly a 10-fold risk of post-LVAD VA.S7.7.3-2 S7.7.3-4 In many of the initial studies demonstrating ICD benefit, older pulsatile LVAD devices were in use.S7.7.3-2,S7.7.3-5 Studies of ICD use with the newer, continuous flow LVADs have inconsistently shown benefit.S7.7.3-1,S7.7.3- Of note, approximately 2 of 10 patients with an LVAD develop an LVAD related infection in the first year.S7.7.3-8,S7.7.3-9 7.7.4. ICD Use After Heart Transplantation Recommendation for ICD Use After Heart Transplantation References that support the recommendation are summarized in Online Data Supplement 37. COR LOE Recommendation IIb B-NR In patients with a heart transplant and severe allograft vasculopathy with LV dysfunction, an ICD may be reasonable if meaningful survival of greater than 1 year is expected.S7.7.4-1 S7.7.4-3 Recommendation-Specific Supportive Text 1. Development of disease in the transplanted heart places some patients at an increased risk of SCD that has ranged from 10% to 35% in Both rejection and a decreased LVEF are predictors of SCD. The mechanisms underlying SCD in patients with a heart transplant include damage to the conduc- tion system itself and VA due to coronary vas- culopathy or during episodes of acute rejection.


The mechanisms underlying SCD in patients with a heart transplant include damage to the conduc- tion system itself and VA due to coronary vas- culopathy or during episodes of acute rejection. Several small case series observing appropriate ICD termination of VA suggest that an ICD can be beneficial in selected patients, particularly those with severe allograft vasculopathy, unex- plained syncope, a history of SCA, and severe LV Additionally, a patient with severe allograft vasculopathy who is being consid- ered for retransplant may be appropriate for an ICD as a bridging device. Secondary prevention indications for an ICD in patients with a heart transplant are identical to those in other patients. 7.8. Neuromuscular Disorders Recommendations for Neuromuscular Disorders References that support the recommendations are summarized in Online Data Supplement 38. COR LOE Recommendations I B-NR In patients with neuromuscular disorders, primary and secondary prevention ICDs are recommended for the same indications as for patients with NICM if meaningful survival of greater than 1 year is expected.S7.8-1,S7.8-2 IIa B-NR In patients with Emery-Dreifuss and limb- girdle type IB muscular dystrophies with progressive cardiac involvement, an ICD is reasonable if meaningful survival of greater than 1 year is expected.S7.8-3 S7.8-8 IIa B-NR In patients with muscular dystrophy, follow- up for development of cardiac involvement is reasonable, even if the patient is asymptomatic at presentation.S7.8-9 S7.8-12 IIb B-NR In patients with myotonic dystrophy type 1 with an indication for a permanent pacemaker, an ICD may be considered to minimize the risk of SCA from VT if meaningful survival of greater than 1 year is expected.S7.8-9,S7.8-13,S7.8-14 Synopsis The muscular dystrophies are a group of inherited diseas- es affecting skeletal and cardiac muscle.


COR LOE Recommendations I B-NR In patients with neuromuscular disorders, primary and secondary prevention ICDs are recommended for the same indications as for patients with NICM if meaningful survival of greater than 1 year is expected.S7.8-1,S7.8-2 IIa B-NR In patients with Emery-Dreifuss and limb- girdle type IB muscular dystrophies with progressive cardiac involvement, an ICD is reasonable if meaningful survival of greater than 1 year is expected.S7.8-3 S7.8-8 IIa B-NR In patients with muscular dystrophy, follow- up for development of cardiac involvement is reasonable, even if the patient is asymptomatic at presentation.S7.8-9 S7.8-12 IIb B-NR In patients with myotonic dystrophy type 1 with an indication for a permanent pacemaker, an ICD may be considered to minimize the risk of SCA from VT if meaningful survival of greater than 1 year is expected.S7.8-9,S7.8-13,S7.8-14 Synopsis The muscular dystrophies are a group of inherited diseas- es affecting skeletal and cardiac muscle. Some present primarily as a NICM (eg, Duchenne, Becker, and limb-gir- dle types 2C, 2F, and 2I), while others present primarily as conduction system degeneration with a variable associa- tion with cardiomyopathy (eg, myotonic dystrophy types 1 and 2, Emery-Dreifuss, limb-girdle type 1B; summa- rized in Table 9).S7.8-15 Because SCD can occur either due to VA or due to bradyarrhythmias from rapid and unpre- dictable progression of conduction system disease, the clinician is faced with the challenge of identifying those patients who would benefit from prophylactic pacemak- CLINICAL STATEMENTS AND GUIDELINES er or ICD implantation. There should be a high level of concern for those patients with muscular dystrophy who present with arrhythmia symptoms.S7.8-15 The current guideline focuses on VA and indications for implantation of an ICD. The indications for permanent pacemaker are discussed in another ACC/AHA/HRS guideline.S7.8-16 Recommendation-Specific Supportive Text 1.


The indications for permanent pacemaker are discussed in another ACC/AHA/HRS guideline.S7.8-16 Recommendation-Specific Supportive Text 1. In general, the indications for an ICD in patients with muscular dystrophy should follow standard ICD recommendations for patients with NICM (see Section 7.2.1 on Secondary Prevention and Section 7.2.2 on Primary Prevention of SCD with NICM). A high index of suspicion for bundle- branch reentrant tachycardia is warranted in patients with myotonic dystrophy who exhibit wide QRS complex tachycardia or tachycardia- 2.


A high index of suspicion for bundle- branch reentrant tachycardia is warranted in patients with myotonic dystrophy who exhibit wide QRS complex tachycardia or tachycardia- 2. In patients with Emery-Dreifuss and limb-girdle type 1B muscular dystrophies associated with Lamin A/C mutations, SCD accounts for about one third of all deaths.S7.8-4 Observational studies show a significant rate of appropriate ICD therapy in patients with cardiac conduction disorders who are gene positive for Lamin A/C mutation even if LV function is preserved.S7.8-3,S7.8-5,S7.8-17 In an obser- vational study in which 38% had isolated skeletal muscular involvement but included patients with conduction defects and other risk factors (includ- ing PR interval >240 ms, left bundle-branch block, NSVT, or bradycardia requiring a permanent pace- maker) life-threatening VAs were relatively com- mon; with 52% of patients receiving appropriate ICD therapy including approximately 40% of those patients with an LVEF 45%.S7.8-3 A study of patients who had Lamin A/C mutation, in which approximately 21% had a skeletal muscular dys- trophy phenotype, SCD and appropriate ICD ther- apy were associated with NSVT, LVEF <45%, male sex, and Lamin A/C nonmissense mutations.S7.8-4 These observational studies support the use of an ICD when a pacing indication is present and likely also when evidence of progressive cardiac involvement such as cardiac conduction defects, NSVT or reduced LVEF is present.S7.8-8 There is a paucity of data regarding the rare form of x-linked recessive Emery-Dreifuss muscular dystrophy (related to the Emerin gene mutation), but arrhythmias may be less frequent than for the Lamin A/C mutations.S7.8-15 3. Cardiac involvement can occur in a number of neuromuscular dystrophies (Table 9). To determine cardiac involvement, a 12-lead ECG and echocar- diogram are important for the initial clinical assess- ment, independent of symptom status.


To determine cardiac involvement, a 12-lead ECG and echocar- diogram are important for the initial clinical assess- ment, independent of symptom status. In general, the more extensive the cardiac involvement, includ- ing evidence of distal conduction disease, ven- tricular dysfunction, and atrial arrhythmias, the more likely a VA will occur. The initial evaluation for myotonic dystrophy patients includes ambula- tory monitoring. In asymptomatic patients, some experts advocate for annual follow-up during the concealed phase of the disease with an annual Table 9. Neuromuscular Disorders Associated With Heart Disease Muscular Dystrophy Inheritance Gene/Protein Affected Primary Cardiac Pathology Frequency of Cardiac Involvement Causes of Death Associated With Sudden Death? Duchenne X-linked recessive Dystrophin NICM >90% Respiratory, HF Yes, uncertain etiology Becker X-linked recessive Dystrophin NICM 60% 75% HF, respiratory Yes, uncertain etiology Limb-girdle type 1B Autosomal dominant Lamin A/C Conduction system disease and NICM >90% Sudden, HF Yes Limb-girdle type 2C-2F Autosomal recessive Sarcoglycan NICM <25% Respiratory, HF Uncertain Limb-girdle type 2I Autosomal recessive Fukutin-related protein NICM 20% 80% Respiratory, HF Uncertain Myotonic type 1 Autosomal dominant CTG repeat expansion Conduction system disease and NICM sudden, HF 30% of deaths, uncertain bradycardia versus tachycardia Myotonic type 2 Autosomal dominant CCTG repeat expansion Conduction system disease 10% 25% Normal causes Reported Emery-Dreifuss X-linked and autosomal dominant or recessive Emerin, Lamin A/C Conduction system disease and NICM >90% Sudden, HF Yes Facioscapulohumeral Autosomal dominant D4Z4 repeat contraction Possibly conduction disease 5% 15% Normal causes, respiratory rarely Not reported HF indicates heart failure; and NICM, nonischemic cardiomyopathy. Adapted with permission from Groh, et al.S7.8 15 CLINICAL STATEMENTS AND GUIDELINES 12-lead ECG to screen for development of conduc- tion abnormalities.


Adapted with permission from Groh, et al.S7.8 15 CLINICAL STATEMENTS AND GUIDELINES 12-lead ECG to screen for development of conduc- tion abnormalities. However, the optimal frequency of electrocardiographic screening is unknown.S7.8-18 Once cardiac involvement is present, either on the basis of conduction delay, atrial arrhythmias, or ventricular dysfunction, a low threshold for investi- gating symptoms or electrocardiographic findings by the clinician to determine the need for pace- maker implantation, invasive electrophysiological studies, or ICD implantation is optimal. 4. Up to one third of deaths in myotonic dystrophy patients are sudden.S7.8-9 Although commonly attributed to conduction block and asystole, SCD due to VT/VF has been recognized in patients with functioning permanent pacemakers, and spontane- ous VA have been documented in some.S7.8-13,S7.8-19 The risk of SCD in patients with pacemakers sug- gests that an ICD may be preferred to a pacemaker. However, these patients are also at high risk of respiratory failure as a competing cause of death. Therefore, in patients with severe skeletal muscle involvement, a pacemaker or ICD may not improve A shared decision-making approach to selecting ICD or pacing therapy is warranted. Compared with myotonic type 1 patients, myo- tonic dystrophy type 2 patients are not well studied but may also benefit from the same approach. 7.9. Cardiac Channelopathies Recommendations for Cardiac Channelopathies References that support the recommendations are summarized in Online Data Supplement 39.


Cardiac Channelopathies Recommendations for Cardiac Channelopathies References that support the recommendations are summarized in Online Data Supplement 39. COR LOE Recommendations I B-NR In first-degree relatives of patients who have a causative mutation for long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, or Brugada syndrome, genetic counseling and mutation-specific genetic testing are I B-NR In patients with a cardiac channelopathy and SCA, an ICD is recommended if meaningful survival of greater than 1 year is Synopsis Implantation of an ICD in asymptomatic low-risk pa- tients with a cardiac channelopathy for a positive family history of SCD as the sole indication is unsupported by Recommendation-Specific Supportive Text 1. Clinical screening of first-degree relatives of patients with inherited arrhythmia syndromes is crucial to identifying affected family mem- bers. Due to the increased risk of adverse car- diac events in genotype positive patients with long QT syndrome, catecholaminergic poly- morphic ventricular tachycardia, and Brugada syndrome, targeted screening for the identified family-specific mutation can identify individuals who are at risk for these adverse outcomes.S7.9- Screening ECGs may be insufficient for diagnosis, because the resting ECG in patients with catecholaminergic polymorphic ventricular tachycardia is normal, and as many as 25% of genotype-positive patients with long QT syn- drome have QTc intervals 440 ms.S7.9-2 Due to the increased risk of adverse cardiac events in young patients with long QT syndrome and catecholaminergic polymorphic ventricular screening infants and young children is particularly important to guide therapy and institute preventive measures, including the avoidance of possible provoca- tive medications (www.crediblemeds.org).S7.9-23 However, because up to 15% of mutations pre- viously associated with catecholaminergic poly- morphic ventricular tachycardia do not appear to cause disease,S7.9-24 caution is advised to avoid unnecessary treatment or sports restriction in phenotype-negative catecholaminergic polymor- phic ventricular tachycardia mutation positive individuals.


Due to the increased risk of adverse car- diac events in genotype positive patients with long QT syndrome, catecholaminergic poly- morphic ventricular tachycardia, and Brugada syndrome, targeted screening for the identified family-specific mutation can identify individuals who are at risk for these adverse outcomes.S7.9- Screening ECGs may be insufficient for diagnosis, because the resting ECG in patients with catecholaminergic polymorphic ventricular tachycardia is normal, and as many as 25% of genotype-positive patients with long QT syn- drome have QTc intervals 440 ms.S7.9-2 Due to the increased risk of adverse cardiac events in young patients with long QT syndrome and catecholaminergic polymorphic ventricular screening infants and young children is particularly important to guide therapy and institute preventive measures, including the avoidance of possible provoca- tive medications (www.crediblemeds.org).S7.9-23 However, because up to 15% of mutations pre- viously associated with catecholaminergic poly- morphic ventricular tachycardia do not appear to cause disease,S7.9-24 caution is advised to avoid unnecessary treatment or sports restriction in phenotype-negative catecholaminergic polymor- phic ventricular tachycardia mutation positive individuals. Notably, some patients may prefer not to undergo genetic testing, so genetic coun- seling should focus on this issue. 2. Patients with cardiac channelopathies (ie, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization syndrome, and short QT syndrome) and prior SCA have a significantly increased risk of subsequent SCA or SCD.S7.9-7 S7.9-13,S7.9-25 S7.9-28 Implantation of an ICD reduces the risk of death in high-risk patients.S7.9-9,S7.9-29 S7.9-31 Appropriate ICD therapy for VF/fast VT is reported in 8% to 33% of channelopathy patients, while inappropri- ate shocks and device complications are reported To mini- mize inappropriate shocks, concurrent beta block- ers in long QT syndrome and catecholaminergic polymorphic ventricular tachycardia patients, optimal device programming, and appropriate lead selection are necessary.


Patients with cardiac channelopathies (ie, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization syndrome, and short QT syndrome) and prior SCA have a significantly increased risk of subsequent SCA or SCD.S7.9-7 S7.9-13,S7.9-25 S7.9-28 Implantation of an ICD reduces the risk of death in high-risk patients.S7.9-9,S7.9-29 S7.9-31 Appropriate ICD therapy for VF/fast VT is reported in 8% to 33% of channelopathy patients, while inappropri- ate shocks and device complications are reported To mini- mize inappropriate shocks, concurrent beta block- ers in long QT syndrome and catecholaminergic polymorphic ventricular tachycardia patients, optimal device programming, and appropriate lead selection are necessary. Ventricular pacing without ICD implantation was associated with a significant risk of recurrent SCA or SCD in long QT syndrome patients.S7.9-37 S7.9-39 In selected patients with LQT1 in whom the SCA occurred in the absence of beta-blocker treatment, beta- blocker therapy is offered as an alternative to ICD CLINICAL STATEMENTS AND GUIDELINES implantation in patients who refuse to receive an 7.9.1. Specific Cardiac Channelopathy Syndromes 7.9.1.1. Congenital Long QT Syndrome Recommendations for Long QT Syndrome References that support the recommendations are summarized in Online Data Supplement 40.


Congenital Long QT Syndrome Recommendations for Long QT Syndrome References that support the recommendations are summarized in Online Data Supplement 40. COR LOE Recommendations I B-NR In patients with long QT syndrome with a resting QTc greater than 470 ms, a beta blocker is recommended.S7.9.1.1-1 S7.9.1.1-5 I B-NR In high-risk patients with symptomatic long QT syndrome in whom a beta blocker is ineffective or not tolerated, intensification of therapy with additional medications (guided by consideration of the particular long QT syndrome type), left cardiac sympathetic denervation, and/or an ICD is I B-NR In patients with long QT syndrome and recurrent appropriate ICD shocks despite maximum tolerated doses of a beta blocker, intensification of medical therapy with additional medications (guided by consideration of the particular long QT syndrome type) or left cardiac sympathetic denervation, is recommended.S7.9.1.1-6, I B-NR In patients with clinically diagnosed long QT syndrome, genetic counseling and genetic testing are recommended.S7.9.1.1-17 S7.9.1.1-21 IIa B-NR In patients with suspected long QT syndrome, ambulatory electrocardiographic monitoring, recording the ECG lying and immediately on standing, and/or exercise treadmill testing can be useful for establishing a diagnosis and monitoring the response to therapy.S7.9.1.1-22 S7.9.1.1-29 IIa B-NR In asymptomatic patients with long QT syndrome and a resting QTc less than 470 ms, chronic therapy with a beta blocker is IIb B-NR In asymptomatic patients with long QT syndrome and a resting QTc greater than 500 ms while receiving a beta blocker, intensification of therapy with medications (guided by consideration of the particular long QT syndrome type), left cardiac sympathetic denervation or an ICD may be III: Harm B-NR In patients with long QT syndrome, QT- prolonging medications are potentially Recommendation-Specific Supportive Text 1.


COR LOE Recommendations I B-NR In patients with long QT syndrome with a resting QTc greater than 470 ms, a beta blocker is recommended.S7.9.1.1-1 S7.9.1.1-5 I B-NR In high-risk patients with symptomatic long QT syndrome in whom a beta blocker is ineffective or not tolerated, intensification of therapy with additional medications (guided by consideration of the particular long QT syndrome type), left cardiac sympathetic denervation, and/or an ICD is I B-NR In patients with long QT syndrome and recurrent appropriate ICD shocks despite maximum tolerated doses of a beta blocker, intensification of medical therapy with additional medications (guided by consideration of the particular long QT syndrome type) or left cardiac sympathetic denervation, is recommended.S7.9.1.1-6, I B-NR In patients with clinically diagnosed long QT syndrome, genetic counseling and genetic testing are recommended.S7.9.1.1-17 S7.9.1.1-21 IIa B-NR In patients with suspected long QT syndrome, ambulatory electrocardiographic monitoring, recording the ECG lying and immediately on standing, and/or exercise treadmill testing can be useful for establishing a diagnosis and monitoring the response to therapy.S7.9.1.1-22 S7.9.1.1-29 IIa B-NR In asymptomatic patients with long QT syndrome and a resting QTc less than 470 ms, chronic therapy with a beta blocker is IIb B-NR In asymptomatic patients with long QT syndrome and a resting QTc greater than 500 ms while receiving a beta blocker, intensification of therapy with medications (guided by consideration of the particular long QT syndrome type), left cardiac sympathetic denervation or an ICD may be III: Harm B-NR In patients with long QT syndrome, QT- prolonging medications are potentially Recommendation-Specific Supportive Text 1. Beta blockers reduce adverse cardiac events for long QT syndrome type 1 (Figure 10) (>95%), long QT syndrome type 2 (Figure 11) (>75%), and females with long QT syndrome type 3 (Figure 12) There are limited data regarding efficacy of beta blockers in males with long QT syndrome type 3S7.9.1.1-3,S7.9.1.1-35,S7.9.1.1-36 but, in selected patients, beta blockers can be protective against SCA.S7.9.1.1-36,S7.9.1.1-37 Several observational studies have reported effectiveness for risk reduction in long QT syndrome with pro- pranolol, atenolol, and nadolol with appropriate while meto- prolol appears less effective.S7.9.1.1-41 RCTs to assess comparative efficacy of specific beta blockers are unavailable, although many centers favor the use of nadolol.


Beta blockers reduce adverse cardiac events for long QT syndrome type 1 (Figure 10) (>95%), long QT syndrome type 2 (Figure 11) (>75%), and females with long QT syndrome type 3 (Figure 12) There are limited data regarding efficacy of beta blockers in males with long QT syndrome type 3S7.9.1.1-3,S7.9.1.1-35,S7.9.1.1-36 but, in selected patients, beta blockers can be protective against SCA.S7.9.1.1-36,S7.9.1.1-37 Several observational studies have reported effectiveness for risk reduction in long QT syndrome with pro- pranolol, atenolol, and nadolol with appropriate while meto- prolol appears less effective.S7.9.1.1-41 RCTs to assess comparative efficacy of specific beta blockers are unavailable, although many centers favor the use of nadolol. For long QT syndrome type 1, 1 study reported atenolol reduced risk of VA while nado- lol was not associated with risk reduction.S7.9.1.1-2 For long QT syndrome type 2, nadolol was reported to show superior efficacy.S7.9.1.1-1,S7.9.1.1-2 Patients receiving a beta blocker should undergo ongoing monitoring to assess changes in QTc over time, and adequacy of beta blockade with 2. High-risk patients with long QT syndrome include those with QTc >500 ms, genotypes long QT syndrome type 2 and long QT syn- drome type 3, females with genotype long QT syndrome type 2, <40 years of age, onset of symptoms at <10 years of age, and patients with prior cardiac arrest or recurrent Women with long QT syndrome type 2 are at a higher risk of postpartum cardiac arrest/ and should receive prepreg- nancy counseling. Patients with long QT syn- drome and recurrent syncope while receiving a beta blocker have an increased risk of SCA or appropriate ICD shocksS7.9.1.1-9 and escalation of therapy is warranted to prevent SCD. Earlier stud- ies reported benefit of antibradycardia pacing, Table 10.


Earlier stud- ies reported benefit of antibradycardia pacing, Table 10. Commonly Used QT-Prolonging MedicationsS7.9.1.1-59,S7.9.1.1-62 Examples of QT Prolonging Medications* Antiarrhythmic Medications Psychotropic Medications Antibiotics Others Disopyramide Haloperidol Erythromycin Methadone Procainamide (N-acetylprocainamide) Phenothiazines Pentamidine Probucol Quinidine Citalopram Azithromycin Droperidol Dofetilide Tricyclic Chloroquine Ondansetron Dronedarone antidepressants Ciprofloxacin Ibutilide Fluconazole Sotalol Levofloxacin Amiodarone Moxifloxacin Clarithromycin Itraconazole Ketoconazole *A more complete list is maintained at: www.crediblemeds.org.S7.9.1.1-59 Amiodarone rarely causes torsades de pointes. CLINICAL STATEMENTS AND GUIDELINES with recurrent syncope or cardiac arrest reported In high-risk patients, observational studies sup- port effectiveness of the ICD in preventing SCD, with consideration of left cardiac sympathetic denervation to reduce the frequency of ICD Left cardiac sympa- thetic denervation can reduce VA burden, but up to 27% of high-risk patients experience at least Left cardiac sympathetic denervation may be more effective in patients with long QT syndrome type 1 and long QT syndrome type 3.S7.9.1.1-16 Complications related to left cardiac sympathetic denervation Syncope in patients with long QT syndrome may occur due to vasovagal syncope, noncompliance with medications, or proarrhythmia from concur- Clinical evaluation that incorporates consideration of genotype, QTc inter- val, medication compliance, and shared decision- making regarding the need to change or escalate therapy is important. Use of additional medica- tions is guided by long QT syndrome type. In long Figure 9. Prevention of SCD in patients with long QT syndrome. Colors correspond to Class of Recommendation in Table 1. See Section 7.9.1.1 for discussion. *ICD candidacy as determined by functional status, life expectancy, or patient preference. High-risk patients with LQTS include those with QTc >500 ms, genotypes LQT2 and LQT3, females with genotype LQT2, <40 years of age, onset of symptoms at <10 years of age, and patients with recurrent syncope. ICD indicates implantable cardioverter-defibrillator; LQTS, long QT syndrome; VT, ventricular tachycardia. Figure 10.


ICD indicates implantable cardioverter-defibrillator; LQTS, long QT syndrome; VT, ventricular tachycardia. Figure 10. Long QT syndrome type 1. CLINICAL STATEMENTS AND GUIDELINES QT syndrome type 3 ranolazine, mexiletine, and flecainide shorten the QTc and have been used to reduce recurrent arrhythmias.S7.9.1.1-6,S7.9.1.1-7,S7.9.1.1-10 3. Mexiletine is an additional medication that can be used in patients with long QT syndrome and recurrent ICD shocks. Left cardiac sympa- thetic denervation is associated with a reduc- tion the number of appropriate ICD shocks and VA burden.S7.9.1.1-13 S7.9.1.1-16 Reduction of the QTc to <500 ms after left cardiac sympa- thetic denervation has been correlated with reduced risk of recurrent ICD shocks and fre- quency of symptomsS7.9.1.1-16,S7.9.1.1-52 ; however, SCD or SCA is reported in 3% to 10% of Although arrhythmia burden is often reduced, up to 27% of high-risk patients experience at least Patient out- comes are improved if the left cardiac sym- pathetic denervation is performed in centers with surgical expertise in this procedure. Use of additional medications is guided by long QT Figure 11. Long QT syndrome type 2. Figure 12. Long QT syndrome type 3. CLINICAL STATEMENTS AND GUIDELINES syndrome type. In long QT syndrome type 3, ranolazine, mexiletine, and flecainide shorten the QTc and have been used to reduce recurrent 4. Genetic testing for disease-causing mutations in long QT syndrome offers important diagnos- tic, prognostic, and therapeutic information in addition to the clinical evaluation, and a posi- tive test can facilitate establishing risk for family members. The yield of genetic testing in long QT syndrome phenotype-positive patients is 50% to 86%, with the higher range present in patients with marked QT prolongation or positive family history of SCD.S7.9.1.1-17,S7.9.1.1-21,S7.9.1.1-53 A negative genetic test does not exclude the diagnosis of long QT syndrome, which relies on the clinical evaluation.


The yield of genetic testing in long QT syndrome phenotype-positive patients is 50% to 86%, with the higher range present in patients with marked QT prolongation or positive family history of SCD.S7.9.1.1-17,S7.9.1.1-21,S7.9.1.1-53 A negative genetic test does not exclude the diagnosis of long QT syndrome, which relies on the clinical evaluation. In asymptomatic patients with oth- erwise unexplained prolonged QTc 480 ms on serial ECGs, genetic testing may help con- firm the diagnosis and supplement prognostic information in addition to clinical symptoms and QTc duration.S7.9.1.1-5,S7.9.1.1-18 S7.9.1.1-20,S7.9.1.1-30, 5. In a prospective, observational study of patients with suspected long QT syndrome, patients with a history of syncope or cardiac arrest and either an affected first-degree relative or a borderline or prolonged QTc interval underwent exercise treadmill testing and bicycle exercise, with ECGs recorded before, during, and after exercise, as well as in different positions.S7.9.1.1-27 long QT syn- drome was confirmed by genetic testing in all affected individuals. Among patients with border- line-to-normal resting QTc intervals, prolongation of the 4-minute recovery QTc 445 ms had high sensitivity for correctly identifying patients with long QT syndrome.S7.9.1.1-27 A study in younger patients demonstrated QTc prolongation >460 ms at 7 minutes of recovery predicted long QT syndrome type 1 or long QT syndrome type 2 patients versus controls.S7.9.1.1-23 In a study using burst bicycle exercise, patients with latent long QT syndrome had a significantly greater increase in QTc with exercise than either controls or those with QTc prolongation at baseline.S7.9.1.1-24 These findings can be useful in establishing whether long QT syndrome is present.


Among patients with border- line-to-normal resting QTc intervals, prolongation of the 4-minute recovery QTc 445 ms had high sensitivity for correctly identifying patients with long QT syndrome.S7.9.1.1-27 A study in younger patients demonstrated QTc prolongation >460 ms at 7 minutes of recovery predicted long QT syndrome type 1 or long QT syndrome type 2 patients versus controls.S7.9.1.1-23 In a study using burst bicycle exercise, patients with latent long QT syndrome had a significantly greater increase in QTc with exercise than either controls or those with QTc prolongation at baseline.S7.9.1.1-24 These findings can be useful in establishing whether long QT syndrome is present. Monitoring ade- quacy of beta-blocker therapy using exercise testing can be beneficial, particularly in school- Beta-blocker ther- apy may be associated with a decrease in supine and peak exercise QTc, with the exception of long QT syndrome type 1 patients with C-loop itive patients with long QT syndrome have QTc intervals 440 ms, most commonly patients with long QT syndrome type 1.S7.9.1.1-31,S7.9.1.1-35 Patients with long QT syndrome and normal QTc have a lower risk of VA and SCD compared to those with prolonged QTc,S7.9.1.1-35 but still have an increased risk of SCA or SCD compared with gen- otype-negative, age- and sex-matched general Beta blockers reduce the risk of adverse cardiac events substantially.S7.9.1.1-1 S7.9.1.1-5, During the periods of highest risk in the first 3 decades of treatment with a beta blocker may reduce risk of SCA.S7.9.1.1-26,S7.9.1.1-28,S7.9.1.1-36, Changes in QTc occur over time, particu- larly during puberty and during and after preg- nancy, indicating the need for assessment of QTc on ECG annually or with medication changes, and assessing medication efficacy with exercise testing as feasible. Asymptomatic adult (male) long QT syndrome patients with normal QTc intervals may choose to decline beta-blocker 7.


Asymptomatic adult (male) long QT syndrome patients with normal QTc intervals may choose to decline beta-blocker 7. The risk of adverse cardiac events from VA is influenced by the patient s resting QTc inter- val, age, sex, and long QT syndrome genotype/ mutation. For asymptomatic males with long QT syndrome, the risk of cardiac events is highest in during a time when medication compliance is challeng- ing. Young women with LQT2 and QTc >500 ms are at increased risk of SCAS7.9.1.1-2,S7.9.1.1-11, especially in the 9 months postpartum, and may be candidates for primary prevention ICD placement or use of a 8. The risk of adverse events increases in patients with long QT syndrome with prolongation of the QTc QT-prolonging medications (www.crediblemeds. should not be used in patients with long QT syndrome unless there is no suitable alternative; careful monitoring of the QTc during therapy is recommended, with consideration for discontinuing therapy with marked QTc prolonga- tion. Concurrent use of stimulant or nonstimu- lant attention deficit/hyperactivity medications was associated with an increased risk of syncope/ cardiac arrest in long QT syndrome, particularly but it did not appear to be associated with increased risk in another ret- Episodes of torsades de pointes can be precipitated by exposure to a QT prolonging medication, or hypokalemia induced by diuretics or gastrointestinal illenss. Attention to maintaining normal potassium and magne- sium balance when medications or situations CLINICAL STATEMENTS AND GUIDELINES that promote depletion are encountered is an important component of management. Rare case reports exist of fever prolonging the QT interval in patients with long QT syndrome type 2; fever should be reduced with antipyreticsS7.9.1.1-61 (Table 10). 7.9.1.2. Catecholaminergic Polymorphic Ventricular Tachycardia Recommendations for Catecholaminergic Polymorphic Ventricular Tachycardia References that support the recommendations are summarized in Online Data Supplement 41.


Catecholaminergic Polymorphic Ventricular Tachycardia Recommendations for Catecholaminergic Polymorphic Ventricular Tachycardia References that support the recommendations are summarized in Online Data Supplement 41. COR LOE Recommendations I B-NR In patients with catecholaminergic polymorphic ventricular tachycardia, a beta blocker is recommended.S7.9.1.2-1,S7.9.1.2-2 I B-NR In patients with catecholaminergic polymorphic ventricular tachycardia and recurrent sustained VT or syncope, while receiving adequate or maximally tolerated beta blocker, treatment intensification with either combination medication therapy (eg, beta blocker, flecainide), left cardiac sympathetic denervation, and/or an ICD is IIa B-NR In patients with catecholaminergic polymorphic ventricular tachycardia and with clinical VT or exertional syncope, genetic counseling and genetic testing are Recommendation-Specific Supportive Text 1. Catecholaminergic polymorphic ventricular tachy- cardia is characterized by exertion-related poly- morphic or bidirectional VT (Figure 13), associated with syncope and SCA. SCA/SCD is reported Treatment with beta blockers is associated with a reduction in adverse cardiac events.S7.9.1.2-1,S7.9.1.2-2 Some experts prefer the use of nadolol over other types of beta blockers; direct comparison data among beta blockers are unavailable. Use of a maximally tolerated dose of a beta blocker is important. Small observational studies sug- gest possible benefit of nondihydropyridine calcium channel blockers in the treatment of catecholaminergic polymorphic ventricular 2. Flecainide in combination with a beta blocker can suppress ventricular ectopy by as much as 76% in patients with catecholaminergic poly- morphic ventricular tachycardia during exercise testing or clinical follow-up.S7.9.1.2-2,S7.9.1.2-6,S7.9.1.2-11 For refractory VA, verapamil or propafenone may also be effective.S7.9.1.2-9,S7.9.1.2-10,S7.9.1.2-12 ICD implantation in patients with catecholaminergic polymorphic ventricular tachycardia should be reserved for patients with prior SCA, or patients with refractory VAs on combination medical therapy.


Flecainide in combination with a beta blocker can suppress ventricular ectopy by as much as 76% in patients with catecholaminergic poly- morphic ventricular tachycardia during exercise testing or clinical follow-up.S7.9.1.2-2,S7.9.1.2-6,S7.9.1.2-11 For refractory VA, verapamil or propafenone may also be effective.S7.9.1.2-9,S7.9.1.2-10,S7.9.1.2-12 ICD implantation in patients with catecholaminergic polymorphic ventricular tachycardia should be reserved for patients with prior SCA, or patients with refractory VAs on combination medical therapy. Inappropriate shocks are reported in 20% to 30% of catecholaminergic poly- morphic ventricular tachycardia patients with ICD programming in patients with catecholaminergic polymorphic ventricular tachycardia should be optimized to deliver therapy for VF and to minimize inappro- priate shocks and the risk of potentially fatal Left cardiac sympathetic denervation for catecholaminer- gic polymorphic ventricular tachycardia may reduce the frequency of recurrent ICD shocks although recurrent syncope, SCA, or SCD is reported in 9% to 32% of patients, with other minor complications in 20% to 70% of patients. It is best if the left cardiac sym- pathetic denervation is performed in centers with expertise in this procedure. Intensification of medical therapy or left cardiac sympathetic denervation is important in treating patients who present with recurrent appropriate ICD 3. Genetic testing may be useful to confirm the diagnosis of catecholaminergic polymorphic ventricular tachycardia, which is suggested by the development of bidirectional VT with exertion or stress. Recognition of catechol- aminergic polymorphic ventricular tachycardia as the cause for exertional symptoms should prompt aggressive therapy to prevent the sig- nificant risk of SCD.


Recognition of catechol- aminergic polymorphic ventricular tachycardia as the cause for exertional symptoms should prompt aggressive therapy to prevent the sig- nificant risk of SCD. Therapy for catechol- aminergic polymorphic ventricular tachycardia is not guided by genotype status, but screen- ing of first-degree relatives may be facilitated with genetic testing.S7.9.1.2-20 Ryanodine recep- tor mutations have been reported in 47% of probands, which were de novo mutations Ryanodine genotype status has not correlated with disease severity or response to medications.S7.9.1.2-7 In very young patients presenting with idiopathic VF, muta- tions in calmodulin have been identified and are associated with high lethality.S7.9.1.2-21 S7.9.1.2-24 Studies of proposed pathogenic mutations in catecholaminergic polymorphic ventricular tachycardia genes report up to 15% of variants were present in exome databases of the general population, raising questions as to the mono- genic cause of catecholaminergic polymorphic CLINICAL STATEMENTS AND GUIDELINES 7.9.1.3. Brugada Syndrome Recommendations for Brugada Syndrome References that support the recommendations are summarized in Online Data Supplement 42 and Systematic Review Report.


Brugada Syndrome Recommendations for Brugada Syndrome References that support the recommendations are summarized in Online Data Supplement 42 and Systematic Review Report. COR LOE Recommendations I B-NR In asymptomatic patients with only inducible type 1 Brugada electrocardiographic pattern, observation without therapy is I B-NR In patients with Brugada syndrome with spontaneous type 1 Brugada electrocardiographic pattern and cardiac arrest, sustained VA or a recent history of syncope presumed due to VA, an ICD is recommended if meaningful survival of greater than 1 year is I B-NR In patients with Brugada syndrome experiencing recurrent ICD shocks for polymorphic VT, intensification of therapy with quinidine or catheter ablation is I B-NR In patients with spontaneous type 1 Brugada electrocardiographic pattern and symptomatic VA who either are not candidates for or decline an ICD, quinidine or catheter ablation is IIa B-NR In patients with suspected Brugada syndrome in the absence of a spontaneous type 1 Brugada electrocardiographic pattern, a pharmacological challenge using a sodium channel blocker can be useful for IIb B-NRSR In patients with asymptomatic Brugada syndrome and a spontaneous type 1 Brugada electrocardiographic pattern, an electrophysiological study with programmed ventricular stimulation using single and double extrastimuli may be considered for further risk IIb C-EO In patients with suspected or established Brugada syndrome, genetic counseling and genetic testing may be useful to facilitate cascade screening of SR indicated systematic review. Synopsis Refer to the Systematic Review for the 2017 ACC/ AHA/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death for the complete systematic evidence review for additional data and analyses.S7.9.1.3-15 The results from the question For asymptomatic patients with Brugada syndrome, what is the association be- tween an abnormal EP study and SCD and other ar- rhythmia endpoints?


Synopsis Refer to the Systematic Review for the 2017 ACC/ AHA/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death for the complete systematic evidence review for additional data and analyses.S7.9.1.3-15 The results from the question For asymptomatic patients with Brugada syndrome, what is the association be- tween an abnormal EP study and SCD and other ar- rhythmia endpoints? (Part 1) and the writing commit- tee s review of the totality of the literature were used to frame decision-making. Recommendations that are based on a body of evidence that includes the system- Figure 13. Exercise-induced polymorphic VT in catecholaminergic polymorphic ventricular tachycardia. Recommendations for Brugada Syndrome (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES atic review conducted by the ERC are denoted by the superscript SR (eg, LOE: B-RSR ). Factors identified as potential triggers of VF and SCA in Brugada syndrome include some psychotropic medica- tions, and anesthetic agents, cocaine, excessive alcohol intake, and fever (www.brugadadrugs.org).S7.9.1.3-21,S7.9.1.3-22 These agents should be avoided, and fever war- rants early and aggressive measures to reduce Recommendation-Specific Supportive Text 1. The risk of major adverse cardiac events in asymptomatic patients without spontaneous type 1 electrocardiographic changes of Brugada syndrome (Figure 15), or with only medica- tion-induced electrocardiographic changes, A positive family history of Brugada syndrome or SCA is not a signifi- cant predictor of adverse events in Brugada Implantation of an ICD in an asymptomatic patient without a spontaneous type 1 Brugada electrocardiographic has not been shown to confer any benefit. 2. Brugada syndrome is characterized by coved ST elevation in leads V1 or V2 positioned in the second, third, or fourth intercostal space either spontaneously or induced by administration of a sodium channel blocking drug in the absence Figure 14.


Brugada syndrome is characterized by coved ST elevation in leads V1 or V2 positioned in the second, third, or fourth intercostal space either spontaneously or induced by administration of a sodium channel blocking drug in the absence Figure 14. Prevention of SCD in patients with Brugada syndrome. Colors correspond to Class of Recommendation in Table 1. See Section 7.9.1.3 for discussion. *ICD candidacy as determined by functional status, life expec- tancy or patient preference. 1 indicates primary; ECG, electrocardiogram; EP, electrophysiological; ICD implantable cardioverter-defibrillator; SCD, sudden cardiac death; VT, ventricular tachycardia; and VF, ventricular fibrillation. Figure 15. Brugada syndrome. CLINICAL STATEMENTS AND GUIDELINES of other causes of ST elevationS7.9.1.3-24 and nega- tive T waves in the right precordial leads, and is associated with syncope or SCA due to VF, pre- dominantly in young males, although it has been reported in all age groups. The type 1 Brugada ECG with coved ST elevation in right precordial leads may be present spontaneously, during fever or vagotonic states, or after medication challenge with sodium channel blockers. QRS complex fractionation is seen in a minority of patients. Patients with spontaneous coved type ST elevation and a history of syncope or prior SCA are at the highest risk for potentially lethal VA. ICD implantation has been shown to reduce mortality in symptomatic patients with Brugada 3. Ablation of abnormal areas of epicardial late activation in the RV can suppress recur- rent VA as shown in a small number of In these reports, the spontaneous type 1 Brugada pat- tern on ECG may be eliminated in >75% of patients, and recurrences of VT/VF are markedly Experience and follow-up after ablation are limited, and an ICD for patients who have had syncope or SCA is recommended.


Ablation of abnormal areas of epicardial late activation in the RV can suppress recur- rent VA as shown in a small number of In these reports, the spontaneous type 1 Brugada pat- tern on ECG may be eliminated in >75% of patients, and recurrences of VT/VF are markedly Experience and follow-up after ablation are limited, and an ICD for patients who have had syncope or SCA is recommended. A series of patients with Brugada syndrome treated with quinidine had no deaths during a mean follow-up of over 9 years, although adverse effects of quinidine were reported in 38% of patients, these authors felt that quinidine could be used as an alternative to the ICD in selected 4. Observational studies show that quinidine can suppress VF storm in patients with Brugada syn- drome, and a low risk of arrhythmia was observed in a long-term observational study.7.9.1.3-7 No patient treated with quinidine experienced SCD. Adverse effects of quinidine occur in up to 37% of patients. Catheter ablation targeting the epicardial right ventricular areas of abnormality has also been shown to reduce recurrent VF epi- sodes and normalize the ECG.7.9.1.3-9 7.9.1.3-11 5. Administration of procainamide, flecainide, or ajmaline may be useful to provoke type 1 ST elevation in patients suspected to have Brugada syndrome as a cause of symptoms but who do not have a type 1 electrocardiographic pattern at baseline.


Administration of procainamide, flecainide, or ajmaline may be useful to provoke type 1 ST elevation in patients suspected to have Brugada syndrome as a cause of symptoms but who do not have a type 1 electrocardiographic pattern at baseline. Medication challenge should be ter- minated with the development of VA, marked QRS widening, or type 1 Brugada electrocardio- The use of high electrocardiographic electrode positioning in the second and third interspaces for electrocardio- graphic recording improves detection of a type Asymptomatic patients with a family history of Brugada syndrome may be offered sodium channel blocker challenge for diagnostic evaluation, although a positive test does not require chronic therapy due to a low risk in this setting.S7.9.1.3-12 In asymptomatic patients with type 1 Brugada electrocardiographic find- ings, medication challenge does not offer addi- tional diagnostic value. 6. Polymorphic VT/VF induced by programmed stim- ulation has been associated with an increased risk of VA in some patients with spontaneous type The specificity of pro- grammed stimulation for assessing risk decreases with the inclusion of triple extrastimuli.S7.9.1.3-6, The value of programmed stimulation in asymptomatic patients with spontaneous type 1 Brugada ECGs has been the subject of mul- A report found that the prognostic value has decreased over time, possibly as patients with less severe phenotypes have been recognized and Some experts use the results of programmed ventricular stimulation for inform- ing shared decision-making in consideration of the ICD. In symptomatic patients with Brugada syndrome, programmed ventricular stimula- tion for risk stratification does not add anything to the evaluation of the patients as an ICD is 7. The yield of genetic testing in phenotype positive patients is approximately 20% to 30% in Brugada SCN5A variants account for most of this subset of genotype positive Brugada syndrome.


The yield of genetic testing in phenotype positive patients is approximately 20% to 30% in Brugada SCN5A variants account for most of this subset of genotype positive Brugada syndrome. However, 2% to 10% of other- wise healthy individuals host a rare variant of Anegativegenetictestdoes not exclude the diagnosis of Brugada syndrome, which is usually based on electrocardiographic and clinical characteristics. Risk stratification is based on symptoms and clinical findingsS7.9.1.3-32 ; genotype status is not correlated with the risk of adverse events.S7.9.1.3-5,S7.9.1.3-18,S7.9.1.3-19,S7.9.1.3-33 Identification of a pathogenetic mutation may help facilitate recognition of carrier status in fam- ily members, allowing for lifestyle modification and potential treatment. 8. Factors identified as potential triggers of VF and SCA in Brugada syndrome include some psy- chotropic medications, and anesthetic agents, cocaine, excessive alcohol intake, and fever These agents should be avoided and fever warrants early and aggressive measures to reduce tempera CLINICAL STATEMENTS AND GUIDELINES 7.9.1.4. Early Repolarization J-wave Syndrome Recommendations for Early Repolarization Syndrome References that support the recommendations are summarized in Online Data Supplement 43. COR LOE Recommendations I B-NR In asymptomatic patients with an early repolarization pattern on ECG, observation without treatment is I B-NR In patients with early repolarization pattern on ECG and cardiac arrest or sustained VA, an ICD is recommended if meaningful survival greater than 1 year is III: No Benefit B-NR In patients with early repolarization pattern on ECG, genetic testing is not Recommendation-Specific Supportive Text 1. The prevalence of an early repolarization pattern on ECG with J point elevation in the inferior or lateral leads of at least 0.1 mV has been reported to be as high as 5.8% in adultsS7.9.1.4-1 and is more common in males.


The prevalence of an early repolarization pattern on ECG with J point elevation in the inferior or lateral leads of at least 0.1 mV has been reported to be as high as 5.8% in adultsS7.9.1.4-1 and is more common in males. The early repolarization pat- tern was lost during 10-year follow-up in >60% of young males.S7.9.1.4-2 Patients are determined to have an early repolarization syndrome when, in addition to having early repolarization pattern on an ECG, they either have symptoms such as syncope or present with an arrhythmia. When patients present with an early repolarization pat- tern on an ECG, it is important to rule out revers- ible causes such as ischemia. Patients with early repolarization are more susceptible to the devel- opment of VF during acute cardiac ischemia and/ or in the presence of QRS abnormalities due to LV hypertrophy or bundle-branch block.S7.9.1.4-6 S7.9.1.4-8 2. Patients with cardiac arrest or VF in the setting of an electrocardiographic pattern of early repolar- ization are at increased risk for subsequent recur- rent episodes of VF, occurring in at least 40% Antiarrhythmic medications, with the exception of quindine/ hydroquinidine, have limited efficacy in prevent- ing recurrent VA.S7.9.1.4-3,S7.9.1.4-4 3. To date, genetic testing has not reliably identified mutations predisposing to early repolarization.S7.9.1.4-5 7.9.1.5. Short QT Syndrome Recommendations for Short QT Syndrome References that support the recommendations are summarized in Online Data Supplement 44.


Short QT Syndrome Recommendations for Short QT Syndrome References that support the recommendations are summarized in Online Data Supplement 44. COR LOE Recommendations I B-NR In asymptomatic patients with a short QTc interval, observation without treatment is I B-NR In patients with short QT syndrome who have a cardiac arrest or sustained VA, an ICD is recommended if meaningful survival greater than 1 year IIa C-LD In patients with short QT syndrome and recurrent sustained VA, treatment with quinidine can be useful.S7.9.1.5-3,S7.9.1.5-5,S7.9.1.5-6 IIa C-LD In patients with short QT syndrome and VT/ VF storm, isoproterenol infusion can be IIb C-EO In patients with short QT syndrome, genetic testing may be considered to facilitate screening of first-degree relatives.S7.9.1.5-4 Recommendation-Specific Supportive Text 1. The prevalence of short QTc 340 ms is esti- mated to be 5 in 10000 in persons <21 years of age and is more common in An incidental finding of a short QTc 320 ms in an asymp- tomatic patient warrants monitoring and follow-up without prophylactic medication 2. Patients with cardiac arrest in the setting of short QT syndrome are known to be at increased risk for recurrent cardiac arrest.S7.9.1.5-3 S7.9.1.5-5 Approximately 18% of the small number of reported patients with short QT and implanted ICDs have experienced appropriate ICD therapies during short-term follow-up.S7.9.1.5-3,S7.9.1.5-5,S7.9.1.5-6 Therapy with quinidine may reduce the number of ICD shocks.S7.9.1.5-3,S7.9.1.5-5,S7.9.1.5-6 3.


Patients with cardiac arrest in the setting of short QT syndrome are known to be at increased risk for recurrent cardiac arrest.S7.9.1.5-3 S7.9.1.5-5 Approximately 18% of the small number of reported patients with short QT and implanted ICDs have experienced appropriate ICD therapies during short-term follow-up.S7.9.1.5-3,S7.9.1.5-5,S7.9.1.5-6 Therapy with quinidine may reduce the number of ICD shocks.S7.9.1.5-3,S7.9.1.5-5,S7.9.1.5-6 3. Markedly shortened QTc values 300 ms are associated with increased risk of SCD, especially during sleep or rest, in young persons, in whom the median QTc was A clinical score including QTc duration, clinical history of documented polymor- phic VT or VF, unexplained syncope, family history of autopsy-negative SCD or sudden infant death syndrome, and positive genotype results has been proposed to identify patients at increased risk for SCD.S7.9.1.5-4,S7.9.1.5-10 Treatment with quini- dine results in lengthening of the QTc and, in selected patients, may be an alternative to ICD 4. In the setting of electrical storm with refractory VF and short QT syndrome, infusion of isoproterenol can be effective in restoring/maintaining sinus 5. Pathogenic mutations in potassium channels have been identified in approximately 10% to Recommendations for Short QT Syndrome (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES 20% of patients with short QT syndrome includ- Due to the rarity of the disease, genotype/phenotype correlations are unavailable, limiting the use of knowledge of genotype status. 8. VA IN THE STRUCTURALLY NORMAL HEART Recommendations for VA in the Structurally Normal Heart References that support the recommendations are summarized in Online Data Supplement 45.


VA IN THE STRUCTURALLY NORMAL HEART Recommendations for VA in the Structurally Normal Heart References that support the recommendations are summarized in Online Data Supplement 45. COR LOE Recommendations I B-R In patients with symptomatic PVCs in an otherwise normal heart, treatment with a beta blocker or nondihydropyradine calcium channel blocker is useful to reduce recurrent arrhythmias and improve IIa B-R In patients with symptomatic VA in an otherwise normal heart, treatment with an antiarrhythmic medication is reasonable to reduce recurrent symptomatic arrhythmias and improve symptoms if beta blockers and nondihydropyradine calcium channel blockers are ineffective or Synopsis Most idiopathic VA are due to a focal mechanism of triggered activity or abnormal automaticity, some, no- tably interfascicular reentrant LV tachycardias, are due to reentry. The clinical manifestations of idiopathic VA are highly variable and range from benign, asymptom- atic PVCs to sustained VT or even VF. On initial discovery, an evaluation for structural heart disease is warranted with physical examination, an ECG, and imaging, usu- ally with echocardiography. In the absence of any ab- normality or a family history of SCD, further assessment and treatment are guided by symptoms. If the patient is asymptomatic and does not have evidence of a cardiac channelopathy, reassurance as to the benign nature is sufficient. If the arrhythmia is suspected of being suf- ficiently frequent to cause ventricular dysfunction over time, periodic follow-up with reassessment of ventricular function is warranted (see Section 10.8). For mild symp- toms, avoidance of aggravating factors such as excessive consumption of caffeine or sympathomimetic agents, may be sufficient. Therapy with a beta blocker or non- dihydropyradine calcium channel blocker reduces symp- toms for some patients. Class I antiarrhythmic medica- tions can be effective, but those are generally avoided due to concerns for adverse effects.


Class I antiarrhythmic medica- tions can be effective, but those are generally avoided due to concerns for adverse effects. For patients who require arrhythmia suppression for whom antiarrhythmic medications are ineffective, not tolerated, or undesired, catheter ablation can be a highly effective treatment (see Section 9). The ablation strategy is to identify the site of origin manifested by the earliest site of electrical activa- tion or, when this is not feasible, by pace-mapping. The most common site of origin for idiopathic VA is from the right ventricular outflow tract (RVOT) or the ostium of the LV, which is comprised of the oval opening of the LV to which the aorta is attached anteriorly and the left atrium is attached posteriorly. The likely origin can be reasonably predicted from the QRS morphology of the VA, which provides a good indication of the type of ap- proach required and the likelihood of success and risks. Ablation failure is often related to the absence of the VA for mapping at the time of the procedure, or origin of the VA in an inaccessible region of the heart. These foci occasionally produce sustained monomorphic VT.S8-5 S8-7 Recommendation-Specific Supportive Text 1. In a randomized, double-blinded, placebo-con- trolled study of 52 patients with symptomatic VA and a mean PVC count of 21407 1740 beats per 24 hours, atenolol significantly decreased symptom frequency (P=0.03) and PVC count (P=0.001), whereas placebo had no effect on PVC count (P=0.78) or average heart rate (P=0.44).S8-8 A prospective randomized comparison of antiar- rhythmic medications versus catheter ablation, metoprolol or propafenone had modest efficacy to suppress RVOT VA although with a far higher rate of recurrence than catheter ablation.S8-9 2.


In a randomized, double-blinded, placebo-con- trolled study of 52 patients with symptomatic VA and a mean PVC count of 21407 1740 beats per 24 hours, atenolol significantly decreased symptom frequency (P=0.03) and PVC count (P=0.001), whereas placebo had no effect on PVC count (P=0.78) or average heart rate (P=0.44).S8-8 A prospective randomized comparison of antiar- rhythmic medications versus catheter ablation, metoprolol or propafenone had modest efficacy to suppress RVOT VA although with a far higher rate of recurrence than catheter ablation.S8-9 2. In an RCT of 233 patients with 30 PVCs per hour, d-sotalol was shown to reduce frequent PVCs, but only racemic dl-sotalol is presently In a prospective randomized com- parison of antiarrhythmic medications versus catheter ablation, therapy with metoprolol or propafenone was shown to have modest effi- cacy when used to suppress RVOT PVCs although with a far higher rate of recurrence than catheter Nondihydropyridine calcium channel blockers reduce arrhythmias.S8-1,S8-2,S8-11,S8-12 8.1. Outflow Tract and Atrioventricular Annular VA Recommendations for Outflow Tract VA References that support the recommendations are summarized in Online Data Supplement 46. COR LOE Recommendations I B-NR In patients with symptomatic outflow tract VA in an otherwise normal heart for whom antiarrhythmic medications are ineffective, not tolerated, or not the patient s preference, catheter ablation is useful.S8.1-1 S8.1-3 I B-NR In patients with symptomatic outflow tract VT in an otherwise normal heart, a beta blocker or a calcium channel blocker is CLINICAL STATEMENTS AND GUIDELINES Recommendation-Specific Supportive Text 1.


COR LOE Recommendations I B-NR In patients with symptomatic outflow tract VA in an otherwise normal heart for whom antiarrhythmic medications are ineffective, not tolerated, or not the patient s preference, catheter ablation is useful.S8.1-1 S8.1-3 I B-NR In patients with symptomatic outflow tract VT in an otherwise normal heart, a beta blocker or a calcium channel blocker is CLINICAL STATEMENTS AND GUIDELINES Recommendation-Specific Supportive Text 1. In 1 RCT, catheter ablation was superior to anti- arrhythmic medications at suppressing frequent PVCs arising from the RVOT.S8.1-4 Observational studies have shown that radiofrequency cath- eter ablation is effective in the treatment of idio- pathic VA arising from the RVOT and LV outflow Thesiteofablationmaybebelow or above the pulmonic valve in the RVOT.S8.1-9,S8.1-13 Although most RVOT VA can be ablated within the RV, 10% may require ablation within the pulmonic Serious complications are infre- quent. For LV outflow tract VA, the site of ablation below the aortic valve,S8.1-2,S8.1-6 at the aorto-mitral or on the epicardial surface of the LV summit.S8.1-3,S8.1-17,S8.1-18 The mitral and tricus- pid annulae are less common sites of idiopathic VA, but these VA can also be effectively treated with Approximately 10% of idiopathic VA may arise from the summit of the LV. Some can be ablated from the great cardiac vein or the epicardial surface, but others arise from an inaccessible region in close proximity to the left coronary artery precluding effective ablation.S8.1-14 Intramural sites of origin are infrequent but may require ablation on both the endocardial and epi- cardial surfaces of the LV ostium.S8.1-3 Complications from ablation of outflow tract VA are infrequent, but bleeding complications related to arterial and venous access, pericardial tamponade, and dam- age to the coronary arteries can occur. 2.


Some can be ablated from the great cardiac vein or the epicardial surface, but others arise from an inaccessible region in close proximity to the left coronary artery precluding effective ablation.S8.1-14 Intramural sites of origin are infrequent but may require ablation on both the endocardial and epi- cardial surfaces of the LV ostium.S8.1-3 Complications from ablation of outflow tract VA are infrequent, but bleeding complications related to arterial and venous access, pericardial tamponade, and dam- age to the coronary arteries can occur. 2. In a prospective randomized comparison of anti- arrhythmic medications versus catheter ablation, metoprolol or propafenone was shown to have modest effectiveness when used to suppress RVOT PVCs, though with a far higher rate of recurrence than catheter ablation.S8.1-4 Non-dihydropyradine calcium channel blockers suppress arrhythmia in 8.2. Papillary Muscle VA Recommendation for Papillary Muscle VA (PVCs and VT) References that support the recommendation are summarized in Online Data Supplement 47. COR LOE Recommendation I B-NR In patients with symptomatic VA arising from the papillary muscles for whom antiarrhythmic medications are ineffective, not tolerated, or not the patient s preference, catheter ablation is useful.S8.2-1 S8.2-5 Recommendation-Specific Supportive Text 1. The papillary muscles of the LV or RV can be the site of origin of VA in the presence or absence of struc- tural heart disease.S8.2-1 S8.2-5 Idiopathic left and right ventricular papillary muscle VA are most commonly PVCs and NSVT, and are usually exercise-related and may be induced by intravenous epinephrine or These arrhythmias have a focal, nonreentrant mechanism.


The papillary muscles of the LV or RV can be the site of origin of VA in the presence or absence of struc- tural heart disease.S8.2-1 S8.2-5 Idiopathic left and right ventricular papillary muscle VA are most commonly PVCs and NSVT, and are usually exercise-related and may be induced by intravenous epinephrine or These arrhythmias have a focal, nonreentrant mechanism. Any of the 3 RV papillary muscles may be the site of origin and catheter ablation is usually effective.S8.2-2 In 1 study, successful ablation was achieved in all 8 patients with a reduction in PVC burden from 17 20% to In the left ventricle, the site of origin may be either the posteromedial or the anterolat- eral papillary muscles.S8.2-1,S8.2-4,S8.2-5 Multiple VA QRS morphologies were observed in 47% of patients, and ablation on both sides of the papillary muscle is required in some patients.S8.2-4 Achieving adequate catheter stability can be challenging. Acute abla- tion success is high, but recurrences are more fre- quent than for idiopathic outflow tract VA. Serious complications, including valve injury, appear to be infrequent. The risks of catheter ablation include bleeding related to arterial and venous access and a low risk of pericardial tamponade. 8.3. Interfascicular Reentrant VT (Belhassen Tachycardia) Recommendations for Interfascicular Reentrant VT (Belhassen Tachycardia) References that support the recommendations are summarized in Online Data Supplement 48. COR LOE Recommendations I B-NR In patients with verapamil-sensitive, idiopathic LVT related to interfascicular reentry for whom antiarrhythmic medications are ineffective, not tolerated, or not the patient s preference, catheter ablation is I B-NR In patients with sustained hemodynamically tolerated verapamil-sensitive, idiopathic LVT related to interfascicular reentry, intravenous verapamil is recommended for IIa C-LD In patients with recurrent verapamil-sensitive idiopathic LVT, chronic therapy with oral verapamil can be useful.S8.3-7 S8.3-10 Recommendation-Specific Supportive Text 1.


COR LOE Recommendations I B-NR In patients with verapamil-sensitive, idiopathic LVT related to interfascicular reentry for whom antiarrhythmic medications are ineffective, not tolerated, or not the patient s preference, catheter ablation is I B-NR In patients with sustained hemodynamically tolerated verapamil-sensitive, idiopathic LVT related to interfascicular reentry, intravenous verapamil is recommended for IIa C-LD In patients with recurrent verapamil-sensitive idiopathic LVT, chronic therapy with oral verapamil can be useful.S8.3-7 S8.3-10 Recommendation-Specific Supportive Text 1. Idiopathic LVT is due to reentry involving a portion of the LV Purkinje system, usually the left posterior fascicle as the retrograde limb of the circuit and an incompletely defined segment of LV tissue as the anterograde limb, a portion of which is verapamil CLINICAL STATEMENTS AND GUIDELINES These VTs are typically sustained with a QRS that has a right bundle-branch block configuration with a superior axis. Less frequently an inferior axis VT or a relatively narrow QRS VT occurs as a result of alternate reentry paths, also involving a part of the Purkinje system. Beta block- ers or verapamil typically terminate these arrhyth- mias, but they fail to prevent recurrences in some The target of catheter ablation for the most common form is usually the distal insertion of the anterograde limb of the Purkinje system along the inferior portion of the LV septum near its junc- tion with the left posterior fascicle. Catheter abla- tion is acutely successful in >90% of patients with a risk of recurrence of approximately 10%. This VT may resemble fascicular VA that are due to a focal mechanism in the left anterior or left posterior fas- cicles of the LV His-Purkinje system. These fascicular arrhythmias usually have a focal mechanism with the target of catheter ablation being the site of earliest electrical activation recorded with a presystolic fas- cicular potential.


These fascicular arrhythmias usually have a focal mechanism with the target of catheter ablation being the site of earliest electrical activation recorded with a presystolic fas- cicular potential. Catheter ablation is highly effective for intrafascicular and fascicular VA. Serious compli- cations are infrequent and include bleeding at the site of arterial or venous access and a small risk of bundle branch block or atrioventricular block. 2. Idiopathic LVT is based on reentrant mechanism involving tissue with slow conduction properties along the LV septum as the anterograde limb and the normal left posterior fascicle of the His- Purkinje system as the retrograde limb. The slow conduction zone is verapamil-sensitive.S8.3-3 S8.3-6 These arrhythmias typically have a right bundle- branch block morphology with superior axis, though reversal of the circuit may produce a rela- tively narrow QRS during VT. Verapamil typically terminates these arrhythmias in the anterograde slow conduction zone.S8.3-3 S8.3-6 3. Although no RCTs have been published, the chronic use of oral verapamil for verapamil-sen- sitive idiopathic LVT has been reported to control this tachycardia in many patients, including both adults and children.S8.3-5,S8.3-8 S8.3-10 8.4. Idiopathic Polymorphic VT/VF Recommendations for Idiopathic Polymorphic VT/VF References that support the recommendations are summarized in Online Data Supplement 49. COR LOE Recommendations I B-NR In young patients (<40 years of age) with unexplained SCA, unexplained near drowning, or recurrent exertional syncope, who do not have ischemic or other structural heart disease, further evaluation for genetic arrhythmia syndromes is I B-NR In patients resuscitated from SCA due to idiopathic polymorphic VT or VF, an ICD is recommended if meaningful survival greater than 1 year is expected.S8.4-9 S8.4-13 I B-NR For patients with recurrent episodes of idiopathic VF initiated by PVCs with a consistent QRS morphology, catheter ablation is useful.S8.4-11,S8.4-14 Recommendation-Specific Supportive Text 1.


COR LOE Recommendations I B-NR In young patients (<40 years of age) with unexplained SCA, unexplained near drowning, or recurrent exertional syncope, who do not have ischemic or other structural heart disease, further evaluation for genetic arrhythmia syndromes is I B-NR In patients resuscitated from SCA due to idiopathic polymorphic VT or VF, an ICD is recommended if meaningful survival greater than 1 year is expected.S8.4-9 S8.4-13 I B-NR For patients with recurrent episodes of idiopathic VF initiated by PVCs with a consistent QRS morphology, catheter ablation is useful.S8.4-11,S8.4-14 Recommendation-Specific Supportive Text 1. When combined with clinical evaluation, genetic testing can provide a diagnosis in up to 13% to 60% of younger (<40 years of age) survivors with the most common genotypes identified associated with long QT syndrome, catecholaminergic polymorphic ventricular tachy- cardia, and Brugada syndrome.S8.4-8 Drowning/ near drowning events are particularly associated with LQT1 and catecholaminergic polymorphic ventricular tachycardia; genetic mutations in long QT syndrome and catecholaminergic polymorphic ventricular tachycardia have been identified in 23% of patients with unexplained near-drown- exertion-related cardiac arrest, particularly in children, may be related to long QT syndrome, catecholaminer- gic polymorphic ventricular tachycardia, or to calmodulin/triadin-mediated long QT syndrome/ catecholaminergic polymorphic ventricular tachy- cardia mutations, which may require additional specialized genetic testing.S8.4-1,S8.4-2,S8.4-4,S8.4-16 S8.4-18 Single-driver auto crashes should prompt the consideration of arrhythmic causes. The yield of genetic testing is higher if a family history of SCD at a young age is present. Referral to specialized genetic testing centers is important if local exper- tise is unavailable. 2.


Referral to specialized genetic testing centers is important if local exper- tise is unavailable. 2. VF in the absence of identifiable structural heart disease or known genetic arrhythmia syndromes such as catecholaminergic polymorphic ventricu- lar tachycardia, long QT syndrome, short QT syn- drome, Brugada syndrome, or J wave syndromes is usually the result of short coupled PVCs arising from the Purkinje system in either the right or left ventricles or, less commonly, from the ventricular The recurrence risk after resuscitation of idiopathic VF is very high.S8.4-12 Among 38 consecutive patients from 6 different centers who underwent ablation of primary idio- pathic VF initiated by short coupled PVC, 87% had experienced 2 VF episodes in the preceding Because idiopathic VF is associated with Recommendations for Idiopathic Polymorphic VT/VF (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES a very high risk of recurrent VF, an ICD is indi- cated to prevent SCD. Catheter ablation of the triggering focus has proved to be highly effective in eliminating the repetitive PVCs which induce VF in these patients.S8.4-11 During a median post- procedural follow-up of 63 months, 7 (18%) of 38 patients undergoing catheter ablation of idio- pathic VF induced by short coupled PVCs experi- enced VF recurrence at a median follow-up of 4 months. Five of these 7 patients underwent repeat ablation without VF recurrence. Thus, although catheter ablation is very effective in idiopathic VF, the recurrence risk remains substantial after an apparently successful procedure and the patient should be protected with an ICD. The subcuta- neous ICD may not be a good therapy for these patients due to the higher risk of T-wave over- sensing seenin this population; however, data are 3.


The subcuta- neous ICD may not be a good therapy for these patients due to the higher risk of T-wave over- sensing seenin this population; however, data are 3. Idiopathic VF may be initiated by PVCs that arise from the outflow tracts or the His-Purkinje system within either the right ventricle or left Some patients have clusters of VF episodes (electrical storm) that typi- cally present as PVCs initiating polymorphic VT/VF. The PVCs usually have a consistent QRS morphol- ogy and a short coupling interval and can be tar- geted for ablation to control the arrhythmia.S8.4-11 For PVCs from the Purkinje system, the ablation target is a high-frequency Purkinje potential pre- ceding the PVCs. When episodes are induced by short-coupled PVCs arising from the outflow tracts, the ablation target is the site of earliest ventricular activation. Patients with idiopathic VF often have periods of frequent VT/VF interspersed with peri- ods of relative quiescence.S8.4-11,S8.4-14 To maximize the probability of successful ablation, the proce- dure is best performed during periods of frequent PVCs. Less-frequent episodes of VF may be ame- nable to ablation if frequent PVCs with a consis- tent QRS morphology are present. When the PVCs can be identified, ablation is highly successful, but late recurrences are observed in approximately 10% of patients such that implantation of an ICD is prudent even if ablation is acutely successful. The risks of catheter ablation include bleeding at the site of arterial or venous access and a small risk of pericardial tamponade. Therapy with quinidine acutely and chronically can suppress recurrent VF episodes in some patients.S8.4-22 9. PVC-INDUCED CARDIOMYOPATHY Recommendations for PVC-Induced Cardiomyopathy References that support the recommendations are summarized in Online Data Supplement 50.


PVC-INDUCED CARDIOMYOPATHY Recommendations for PVC-Induced Cardiomyopathy References that support the recommendations are summarized in Online Data Supplement 50. COR LOE Recommendations I B-NR For patients who require arrhythmia suppression for symptoms or declining ventricular function suspected to be due to frequent PVCs (generally >15% of beats and predominately of 1 morphology) and for whom antiarrhythmic medications are ineffective, not tolerated, or not the patient s preference, catheter ablation is useful.S9-1,S9-2 IIa B-NR In patients with PVC-induced cardiomyopathy, pharmacological treatment (eg, beta blocker, amiodarone) is reasonable to reduce recurrent arrhythmias and improve symptoms and LV function.S9-3,S9-4 Recommendation-Specific Supportive Text 1. Frequent PVCs (usually >15% of the total num- ber of beats) may produce a reversible form of However, it is sometimes difficult to ascertain whether the PVCs caused LV dysfunction or whether progressive LV dysfunc- tion caused frequent PVCs. LV dysfunction has been associated with greater PVC burden (>10% and usually >20%), NSVT, a retrograde P-wave after the PVCs, and interpolated PVCs.S9-6,S9-15 In a prospective study of catheter ablation for PVC-induced cardiomyopathy, ablation was com- pletely successful in 80% of patients.S9-19 LV func- tion normalized within 6 months in 82% of the 22 patients who had depressed ventricular dys- function at baseline. Thus, frequent PVCs may be a reversible cause of LV dysfunction that can be effectively treated with catheter ablation. It is often difficult to determine if apparent LV dys- function reflects impaired LV function or inability to accurately assess LV function due to the fre- quent ectopic activity. In patients who have a high density of PVCs with normal ventricular function, optimal treatment and surveillance for prevention and detection of decline in ventricular function have not been established. 2.