For patients with life-threatening VA, observa- tional studies show that patients undergoing coronary artery bypass graft (CABG) had substan- tially better survival after accounting for other The risk of SCD appears compara- ble for patients with complex ischemic heart disease For patients with low LVEF and ischemic heart disease amenable to CABG, the risk of SCD is lower with CABG than medical therapy.S5.5-2,S5.5-7 Observational studies show an association between a lower likelihood of death with revascularization for survivors of SCA and CABGS5.5-3 Revascularization alone is usually insufficient to prevent recurrence of sustained monomorphic VT; further evaluation for inducible VT is generally con- sidered if ventricular function is depressed and/or scar is present. 2. Anomalous aortic origin of the coronary arter- ies is detected in approximately 1% of patients undergoing routine coronary angiography, and <0.2% of children and adolescents under- Although ischemic heart disease is detected in as many as 24% to 55% of SCD cases in young patients <35 years anomalous aortic origin of the coronary arteries is an important cause of SCD in the young, reported in 10% to 17% of patients included in postmortem studies.S5.5-10,S5.5-11 Anomalous origin of the coronary arteries can be identified by echocardiography, invasive coronary angiography, CT angiography or cardiac MRI. In patients with SCA or life-threatening VA presumed CLINICAL STATEMENTS AND GUIDELINES related to ischemia caused by anomalous origin of a coronary artery, repair or revascularization is performed to alleviate ischemia and reduce the recurrence of VA.S5.5-6,S5.5-7,S5.5-12 S5.5-14 5.5.1. Surgery for Arrhythmia Management Recommendation for Surgery for Arrhythmia Management References that support the recommendation are summarized in Online Data Supplement 12. COR LOE Recommendation IIb C-LD In patients with monomorphic VT refractory to antiarrhythmic medications and attempts at catheter ablation, surgical ablation may be Recommendation-Specific Supportive Text 1. Cardiac surgery as a standalone procedure for VT is rarely performed, but has a role in some highly symptomatic patients, when antiarrhyth- mic medications and catheter ablation fails or are not possible, particularly if the failure of abla- tion is due to an arrhythmia arising from an area that is inaccessible to catheter ablation, such as deep in the myocardium, beneath epicardial fat, or near the coronary arteries. Surgical ablation of tachycardia can also be performed at the time of other cardiac surgical interventions, such as dur- ing surgical resection of large aneurysms due to prior MI in which the border zone is often a sub- strate for VT, or placement of an LV assist device The procedure requires detailed characterization of the arrhythmia usually with preoperative imaging and mapping, therefore, surgical ablation is best undertaken at tertiary referral centers and with collaboration between experienced surgeons and electrophysiologists. 5.6. Autonomic Modulation Recommendations for Autonomic Modulation References that support the recommendations are summarized in Online Data Supplements 13 and 14. COR LOE Recommendations IIa C-LD In patients with symptomatic, non life- threatening VA, treatment with a beta blocker is reasonable.S5.6-1 IIb C-LD In patients with VT/VF storm in whom a beta blocker, other antiarrhythmic medications, and catheter ablation are ineffective, not tolerated, or not possible, cardiac sympathetic denervation may be Synopsis Sympathetic activation is proarrhythmic and parasym- pathetic activation is generally antiarrhythmic in VT/VF. Modulating the autonomic nervous system for the pur- pose of preventing arrhythmias is an emerging thera- peutic modality. For the prevention of VA, autonomic modulation can be done either through interruption of sympathetic outflow to the heart, pharmacological beta blockade, or through stimulation of the parasym- pathetic pathway (eg, vagal nerve stimulators, spinal cord stimulators). Although autonomic modulation has proven efficacy for certain conditions such as long QT syndrome and catecholaminergic polymorphic ventricu- lar tachycardia (see Section 7.9), evidence is limited for its applicability to the broader group of VA, but studies are ongoing. Currently, there are limited data on the role of vagal nerve stimulators and spinal cord stimula- tors for the prevention of VA/SCD in humans, and thus no formal recommendation could be supported.S5.6-5 Recommendation-Specific Supportive Text 1. Many patients with non life-threatening VA require only reassurance, but others have symp- toms that warrant therapy. A small RCT of patients with symptomatic VA demonstrated a significant reduction in the arrhythmic burden 2. VT/VF storm causes significant morbidity and is associated with increased mortality. For VT/ VF storm refractory to treatment (medications, catheter ablation), cardiac sympathetic denerva- tion has been shown in several small, observa- to reduce the arrhythmia burden. This has been shown for left or bilateral cardiac sympathetic denervation, and it has been suggested that bilateral cardiac sympathetic denervation may be superior.S5.6-3 Although data are limited, the significant morbid- ity and limited options in these patients make car- diac sympathetic denervation a reasonable option in selected patients. 6. Acute Management of Specific VA Recommendations for Management of Cardiac Arrest References that support the recommendations are summarized in Online Data Supplements 15 and 16. COR LOE Recommendations I A CPR should be performed in patients in cardiac arrest according to published basic and advanced cardiovascular life support I A In patients with hemodynamically unstable VA that persist or recur after a maximal energy shock, intravenous amiodarone should be administered to attempt to achieve a stable rhythm after further CLINICAL STATEMENTS AND GUIDELINES I A Patients presenting with VA with hemodynamic instability should undergo direct current cardioversion.S6-1 S6-3 I B-NR In patients with polymorphic VT or VF with ST-elevation MI, angiography with emergency revascularization is recommended.S6-7 S6-10 I C-EO Patients with a wide-QRS tachycardia should be presumed to have VT if the diagnosis is unclear. IIa A In patients with hemodynamically stable VT, administration of intravenous procainamide can be useful to attempt to IIa B-R In patients with a witnessed cardiac arrest due to VF or polymorphic VT that is unresponsive to CPR, defibrillation, and vasopressor therapy, intravenous lidocaine can be beneficial.S6-1,S6-4,S6-5,S6-14,S6-15 IIa B-R In patients with polymorphic VT due to myocardial ischemia, intravenous beta blockers can be useful.S6-16,S6-17 IIa B-NR In patients with a recent MI who have VT/VF that repeatedly recurs despite direct current cardioversion and antiarrhythmic medications (VT/VF storm), an intravenous beta blocker can be useful.S6-17,S6-18 IIb A In patients in cardiac arrest, administration of epinephrine (1 mg every 3 to 5 minutes) during CPR may be reasonable.S6-1,S6-19 S6-24 IIb B-R In patients with hemodynamically stable VT, administration of intravenous amiodarone or sotalol may be considered to attempt to III: No Benefit A In patients with cardiac arrest, administration of high-dose epinephrine (>1 mg boluses) compared with standard doses is not III: No Benefit A In patients with refractory VF not related to torsades de pointes, administration of intravenous magnesium is not beneficial.S6- III: Harm B-R In patients with suspected AMI, prophylactic administration of lidocaine or high-dose amiodarone for the prevention of VT is III: Harm C-LD In patients with a wide QRS complex tachycardia of unknown origin, calcium channel blockers (eg, verapamil and diltiazem) are potentially harmful.S6-30,S6-31 Recommendation-Specific Supportive Text 1. The most common electrical mechanisms for car- diac arrest are VF and pulseless VT, but substan- tial numbers of cardiac arrests begin as severe bradyarrhythmias or asystole. Survival is better for patients presenting with VT or VF than for those with bradyarrhythmic or asystolic mechanisms.S6-32 Rapid arrival of paramedical personnel is the major determinant of survival. A number of strat- egies for responding to unexpected cardiac arrest, including rapid defibrillation and initiation of CPR for a witnessed cardiac arrest, have improved sur- vival probabilities for cardiac arrest victims.S6-2,S6-3 Nonetheless, the absolute number and propor- tion of survivors remain low, except in unique circumstances where there is an extraordinarily rapid response time to victims in VF or VT such as in monitored intensive care units, where sur- vival is >90%.S6-33 S6-36 Survival decreases rapidly after the initial 2 minutes from the onset of car- diac arrest, so that by 4 to 5 minutes, survival may be 25%, and by 10 minutes it is 0%.S6-33,S6-35,S6-36 Advanced life support activities, other than those directly related to cardioversion and defibrillation for control of tachyarrhythmias, have led to the generation of comprehensive protocols to guide responders. These AHA documents cover the broad expanse of clinical circumstances and con- siderations of mechanisms.S6-1,S6-37 2. Paramedic administration of amiodarone after at least 3 failed shocks and administration of epi- nephrine improved hospital admission rates when compared with placeboS6-6 or 1.5 mg/kg lido- in RCTs in adults with out-of-hospital cardiac arrest due to refractory VF or polymorphic VT, although survival to hospital discharge and survival with favorable neurologic outcome were not improved with amiodarone or lidocaine.S6-5 However, in the subset of patients with witnessed cardiac arrest due to initial shock-refractory VF or pulseless VT, survival to hospital discharge after amiodarone administration was higher than with The administration of procainamide in out-of-hospital cardiac arrest due to VF or pulse- less VT has been associated with more shocks, more pharmacologic interventions, longer resus- citation times, and lower survival.S6-38 3. VA with hemodynamic instability, including VF and pulseless monomorphic or polymorphic VT, causes loss of consciousness and leads to death if untreated. A short time to direct current car- dioversion is the major determinant of sur- vival, and defibrillation should be performed as quickly as possible. CPR is used until a perfusing rhythm is restored. If defibrillation is unsuccess- ful in returning spontaneous circulation, respond- ers follow advanced cardiovascular life support 4. Quickly identifying and treating patients with out-of-hospital cardiac arrest related to acute cor- onary occlusion is associated with improved sur- vival and better functional recovery.S6-37 Coronary occlusion as a cause of cardiac arrest is not reli- ably predicted by clinical and electrocardiographic Recommendations for Management of Cardiac Arrest (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES and emergency coronary angiogra- phy should be considered (rather than later in the hospital stay or not at all) for unstable patients with a suspected cardiac etiology regardless of whether the patient is comatose or awake.S6-9,S6-39 In 1 observational study of patients resuscitated from SCA who did not have ST elevation and had angiography, one third were found to have a cul- prit lesion and coronary intervention appeared to be associated with a greater likelihood of favor- able neurologic outcome.S6-10 5. The initial management of any tachycardia should proceedaccordingtopublishedAHAadvancedcar- diovascular life support guidelines.S6-40 Immediate cardioversion should be performed for hemody- namic instability at presentation or if it develops subsequently. An ECG should be obtained for sta- ble rhythms. Wide-complex tachycardias, defined by a QRS duration 0.12 s,S6-37 can be due to VT, SVT with aberrancy, preexcited tachycardia, or a paced rhythm such as pacemaker-mediated tachycardia. An irregular wide-complex tachycar- dia may be AF with aberrancy, preexcited AF (ie, AF using an accessory pathway for anterograde conduction), atrial flutter, or VT.S6-37 A diagnosis should be established, and consultation with an arrhythmia expert considered.S6-37 6. In 1 study, amiodarone was more effective than lidocaine in terminating incessant VT with improved survival at 24 hours.S6-26 For patients with recurrent, stable VT not in the setting of an AMI, intravenous procainamide has been shown to be superior to lidocaine for terminat- ing the arrhythmia.S6-11 One randomized trial of 62 patients found procainamide superior to amio- darone for termination of stable VT.S6-13 Adverse events, including hypotension were more com- mon with amiodarone, but the difference was not statistically significant. Procainamide and its metabolite n-acetylprocainamide have potassium channel blocking properties that may prolong the QT interval. In patients who already have QT pro- longation, administration of procainamide may further prolong the QT interval and lead to tors- ades de pointes.S6-11,S6-12,S6-26 7. Intravenous lidocaine is an alternative antiar- rhythmic medication of long-standing and widespread familiarity. Compared with no antiarrhythmic medication, lidocaine did not consistently increase a return of spontaneous circulation after defibrillation and was not asso- ciated with improvement in survival to hospital In prospective, blinded, RCTs, lidocaine was less effective than amiodarone in improving hospital admission rates after out-of- hospital cardiac arrest due to shock-refractory VF or polymorphic VT; but there were no differences between the 2 medications in survival to hospital However, in the subset of patients with witnessed SCA due to initial shock- refractory VF or pulseless VT, a subgroup analysis showed that survival to hospital discharge with lidocaine was better than with placebo.S6-5,S6-42 8. In a large meta-analysis of antiarrhythmic medi- cations in the setting of AMI, beta blockers were associated with a significant reduction Beta blockers can be effective in suppressing recurrent VF in patients with recent MI, with an associated improvement in 9. In patients with recurrent VT/VF (VT/VF storm) in the setting of a recent MI that is refractory to ami- odarone and/or lidocaine and repeated cardiover- sion, administration of a beta blocker has been shown to improve survival at 1 week. For those who did not survive, mortality was mostly due to recurrent VF. Survival at 1 year was also better in those treated with a beta blocker.S6-17,S6-18 Other measures to reduce sympathetic tone including sedation and general anesthesia are also often used. 10. Epinephrine produces beneficial effects in patients during cardiac arrest, primarily because of its alpha-adrenergic (ie, vasoconstrictor) effects.S6-1 These alpha-adrenergic effects can increase coronary and cerebral perfusion pressure during CPR. The value and safety of the beta-adrenergic effects of epinephrine are controversial because they may increase myocardial work and reduce One trial assessed short-term and longer-term outcomes when com- paring standard-dose epinephrine to placebo.S6-23 Standard-dose epinephrine was defined as 1 mg given intravenously or intraosseously every 3 to 5 minutes. For both survival to discharge and sur- vival to discharge with good neurologic outcome, there was no benefit with standard-dose epi- nephrine; however, the study was underpowered for analysis of either of these outcomes. There was, nevertheless, improved survival to hospital admission and improved return of spontaneous circulation with the use of standard-dose epi- nephrine. A number of trials have compared out- comes of standard-dose epinephrine with those of high-dose epinephrine. These trials did not demonstrate any benefit for high-dose epineph- rine over standard-dose epinephrine in relation to survival to discharge with a good neurologic recovery, survival to discharge, or survival to hos- 11. Amiodarone was more effective than lidocaine in terminating incessant VT with improved survival CLINICAL STATEMENTS AND GUIDELINES For patients with recurrent, sta- ble VT not in the setting of an AMI, intravenous procainamide has been shown to be superior to lidocaine for terminating the arrhythmia.S6-11 One RCT in 62 patients found procainamide superior to amiodarone for termination of stable VT.S6-13 Adverse events, including hypotension, were more common with amiodarone, but the differ- ence was not statistically signficant. Procainamide and its metabolite n-acetylprocainamide have potassium channel blocking properties that may prolong the QT interval. In patients who already have QT prolongation, administration of procainamide may further prolong the QT inter- val and lead to torsades de pointes.S6-11 A single RCT of 33 patients comparing sotalol with lido- caine for treating patients with hemodynami- cally stable VT showed that VT was terminated in 69% of patients using sotalol and 18% Intravenous sotalol has been approved for use in the United States. Sotalol has potassium channel blocking properties that may prolong the QT interval. In patients who already have QT interval prolongation, administration of sotalol may further prolong the QT interval and lead to torsades de pointes.S6-25 Figure 2. Management of sustained monomorphic VT. Colors correspond to Class of Recommendation in Table 1. See Sections 7, 8.1.3, 8.2.3, and 10 for discussion. *Known history of verapamil sensitive or classical electrocardiographic presentation. ACLS indicates advanced cardiovascular life support; ECG, electrocardiogram; VA, ventricular arrhythmia; and VT, ventricular tachycardia. CLINICAL STATEMENTS AND GUIDELINES 12. Epinephrine may increase coronary and cerebral perfusion pressure during CPR because of its vasoconstrictive effects. High doses of epineph- rine (0.1 to 0.2 mg/kg IV, as opposed to a stan- dard dose of 1 mg) have been studied in RCTs. In out-of-hospital cardiac arrest unresponsive to defibrillation, administration of high-dose epi- nephrine improved survival to hospital admis- sion, but there was no difference compared to standard dose epinephrine in survival to hospital There was also no improvement in Of note, the administra- tion of vasopressin is no longer recommended in the most recent advanced cardiovascular life sup- 13. Magnesium may suppress automaticity, suppress early and late after-depolarizations, and inhibit calcium flux into cardiomyocytes. It is effective in suppressing VA related to acquired long QT syndrome. However, 2 RCTs that investigated the use of intravenous magnesium in patients with cardiac arrest and refractory VF found no In a study of out-of-hospital car- diac arrest, administration of 2 to 4 g magnesium intravenously did not improve survival to hospital In a similar study involving inpa- tient cardiac arrest, magnesium did not improve return of spontaneous circulation, survival to 24 hours, or survival to hospital discharge.S6-28 There are exceptions such as marked hypokale- mia or medication-induced torsades de pointes in which administration of intravenous magne- sium is warranted. 14. Several studies have tested the hypothesis that prophylactic administration of antiarrhythmic medications could reduce the incidence of post- MI VA and lead to better outcomes. One meta- analysis assessed studies in which beta blockers, class I antiarrhythmic agents such as lidocaine and procainamide, and amiodarone were given in the setting of AMI. The routine use of lidocaine and procainamide was associated with increased mor- tality, whereas beta blockers were associated with a significantly lower mortality rate.S6-16 Limited data with amiodarone appeared to be promising, but a subsequent RCT involving 1073 patients found that administration of high-dose amio- darone led to a higher mortality rate, although a moderate dose of amiodarone was not superior 15. With a stable, wide QRS complex tachycardia, differentiation between SVT with aberrancy and VT is often possible by review of the patient s history and the 12-lead ECG during tachycar- dia. Patients with wide QRS complex tachycar- dia and known structural heart disease should be presumed to have VT until proven otherwise. Administration of a calcium channel blocker such as verapamil to a patient with VT may result in severe hypotension or syncope.S6-31 The exception is verapamil-sensitive VT (interfascicu- lar reentry) that occurs in a structurally normal heart; but this is often difficult to recognize on 7. ONGOING MANAGEMENT OF VA AND SCD RISK RELATED TO SPECIFIC DISEASE STATES 7.1. Ischemic Heart Disease 7.1.1. Secondary Prevention of SCD in Patients With Ischemic Heart Disease Recommendations for Secondary Prevention of SCD in Patients With Ischemic Heart Disease References that support the recommendations are summarized in Online Data Supplements 17 and 18. COR LOE Recommendations I B-R In patients with ischemic heart disease, who either survive SCA due to VT/VF or experience hemodynamically unstable VT (LOE: B-R) S7.1.1-1 S7.1.1-4 or stable sustained VT (LOE: B-NR) S7.1.1-5 not due to reversible causes, an ICD is recommended if meaningful survival greater than 1 year is expected. B-NR Value Statement: Intermediate Value (LOE: B-R) A transvenous ICD provides intermediate value in the secondary prevention of SCD particularly when the patient s risk of death due to a VA is deemed high and the risk of nonarrhythmic death (either cardiac or noncardiac) is deemed low based on the patient s burden of comorbidities and I B-NR In patients with ischemic heart disease and unexplained syncope who have inducible sustained monomorphic VT on electrophysiological study, an ICD is recommended if meaningful survival of greater than 1 year is expected.S7.1.1-7 CLINICAL STATEMENTS AND GUIDELINES Recommendation-Specific Supportive Text 1. In the AVID trial,S7.1.1-1 the ICD improved overall sur- vival compared with antiarrhythmic medication ther- apy (primarily amiodarone) in patients who survived SCD or with hemodynamically unstable VT, with a 2-year relative risk reduction in mortality of 27% and an absolute risk reduction of 7%. CIDS (Canadian Implantable Defibrillator Study),S7.1.1-2 which was stopped early after the results of the AVID trial were released, showed a similar, but not statistically signifi- cant, benefit of the ICD over antiarrhythmic medi- cation therapy. A subsequent meta-analysis using data from 3 RCTs showed a statistically significant reduction in both arrhythmic and all-cause mortal- ity with secondary prevention ICDs.S7.1.1-3 In survivors of life-threatening VA that may be due to transient or reversible factors, such as AMI, proarrhythmic medication effects, or electrolyte disturbances, an ICD is not implanted if the cause may be correctable. This is a population of patients that still requires thorough evaluation, treatment, and close follow-up and, as in the AVID registry, mortality was still high in the population that may have had a reversible cause for their arrest.S7.1.1-8 Small increases in troponin present a challenge in selecting patients for an ICD, as it often cannot be determined whether troponin elevation is due to ischemia from VT/VF and resuscitation, in which case an ICD is likely warranted, or an indication that ischemia caused the arrhythmia, in which case pre- vention of ischemia would be the therapeutic focus. ICDs may improve the outcomes of patients with hemodynamically tolerated sustained VT and structural heart diseaseS7.1.1-5 ; however, this has not proved in any RCT. VT ablation has been used as an alternative in selected patients with well-tolerated VT and appears to reduce recurrences, but the impact on long-term mortality is unknown; there is not yet sufficient evidence to recommend this approach as an alternative to ICD implantation.S7.1.1-9,S7.1.1-10 2. Economic outcomes of ICD implantation for second- ary prevention of SCD were assessed in the AVID and CIDS trials,S7.1.1-11,S7.1.1-12 as well as in a simulation and an observational study of Medicare All studies compared ICD recipi- ents with non-ICD recipients, and all found that ICD recipients had longer overall survival and higher lifetime costs of medical care. All studies reported incremental cost-effectiveness ratios between $64000 and $100000 per year of life added by an which is in the range of intermedi- ate value by the benchmarks applied in the ACC/ AHA cost/value statement.S7.1.1-15 3. VAs are an important cause of syncope or near syn- cope in patients with ischemic heart disease, particu- larly those with prior infarction. A study of 70 patients with unexplained syncope who underwent an elec- trophysiological study identified positive findings in 37 patients; 31 with VT. During 3 years of follow-up, patients with a positive electrophysiological study had higher rates of SCD and 3-year total mortality (61% versus 15%, respectively) than those with a negative An ICD is warranted for patients with syncope and inducible sustained monomorphic VT even if they do not otherwise meet criteria for primary prevention (Figure 4). 7.1.1.1. Coronary Artery Spasm Recommendations for Patients With Coronary Artery Spasm References that support the recommendations are summarized in Online Data Supplement 20. COR LOE Recommendations I B-NR In patients with VA due to coronary artery spasm, treatment with maximally tolerated doses of a calcium channel blocker and smoking cessation are indicated to reduce recurrent ischemia and VA.S7.1.1.1-1,S7.1.1.1-2 IIa B-NR In patients resuscitated from SCA due to coronary artery spasm in whom medical therapy is ineffective or not tolerated, an ICD is reasonable if meaningful survival of greater than 1 year is expected.S7.1.1.1-3 S7.1.1.1-6 IIb B-NR In patients resuscitated from SCA due to coronary artery spasm, an ICD in addition to medical therapy may be reasonable if meaningful survival of greater than 1 year is Figure 3. Secondary prevention patients with ischemic heart disease. Colors correspond to Class of Recommendation in Table 1. See Sections 4.3.1 and 7.1.1 for discussion. *Exclude reversible causes. History consistent with an arrhythmic etiology for syncope. ICD candidacy as determined by functional status, life expectancy, or patient preference. EP indicates elec- trophysiological; GDMT, guideline-directed management and therapy; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease; LVEF, left ventricular ejection fraction; pts, patients; SCA, sudden cardiac arrest; SCD, sudden cardiac death; and VT, ventricular tachycardia. CLINICAL STATEMENTS AND GUIDELINES Recommendation-Specific Supportive Text 1. Coronary artery spasm results from vasomotor dysfunction and can occur in the presence or absence of atherosclerotic ischemic heart disease. Vasospasm episodes can lead to VA, syncope, and SCD. Treatment includes risk factor elimina- tion including smoking cessation, and treatment with vasodilators including dihydropyridine cal- cium channel blockers with or without nitrates. A more detailed summary of treatments for coro- nary artery spasm can be found in other guideline 2. Patients with coronary artery spasm who survive an SCA are a high-risk population.S7.1.1.1-5 Recurrent VA, even life-threatening, may be prevented if coronary artery spasm can be effectively addressed with risk factor modification, smoking cessation, and ongo- ing treatment with nitrates and dihydropyridine cal- cium channel blockers.S7.1.1.1-9 However, SCA or VA can recur despite medical therapy or if compliance is poor. Whether a wearable cardioverter-defibrilla- tor may provide protection while medical therapy is being evaluated has not been assessed but is of An ICD can terminate VT/VF initi- ated by spasm, potentially preventing SCD. 3. Patients with coronary vasospasm who survive an SCA are a high-risk population, and some sup- port the use of an ICD in those patients based on the reported event rates from observational stud- even before determining the patient s response to or compliance with medical therapy. Recurrent SCA can occur despite medical therapy. Regardless of the approach, risk factor modifica- tion (eg, illicit drug use), smoking cessation, and ongoing treatment with dihydropyridine calcium channel blockers with or without nitrates repre- sent essential treatments.S7.1.1.1-9 7.1.1.2. Post CABG VT/VF The incidence of sustained VT or VF early after CABG is low, but these VAs are associated with high in-hospital VF occurring very early (intraoperatively or within 24 hours postoperatively) may be due to the transient effects of reperfusion, electrolyte and acid base disturbances, and the use of inotropes. Patients who present with VF or polymorphic VT in the postoperative period more often have associated ischemia, while pa- tients presenting with monomorphic VT usually have an old infarct and ventricular scar.S7.1.1.2-2 Polymorphic VT/VF occurring after CABG warrants a therapeutic approach targeting treatment of myocardial ischemia, including a possible need for assessment of graft patency, as well as identification and treatment of mechanical compli- cations and acute electrolyte or acid base disturbances. Risk factors for occurrence of monomorphic VT early af- ter CABG include prior MI, ventricular scar, LV dysfunc- tion, and placement of a bypass graft across a noncol- lateralized occluded coronary vessel to a chronic infarct Unlike polymorphic VT and VF, sustained monomorphic VT is typically not due to acute ischemia. Many of these patients have inducible sustained VT at electrophysiological study. Management of symptomat- ic VA in the early period after CABG follows the recom- mendations for acute and ongoing management of VT detailed elsewhere in this document. In patients without sustained VT or VF but with LV dysfunction prior to un- dergoing CABG, implantation of an ICD did not improve For patients with LV dysfunction who are undergoing revascularization, there is a possibility that the LV function may improve, so many advocate for re- assessment of the LV function 3 months after revascu- larization before a decision about ICD implantation is For patients with a high burden of NSVT and reduced LVEF, an electrophysiological study may be helpful for risk stratification; those with inducible sus- tained VT may benefit from an ICD.S7.1.1.2-6 The wearable cardioverter-defibrillator may play a role in patients at risk of SCD in the early phase after revascularization to allow time for recovery of ventricular function.S7.1.1.2-7 7.1.2. Primary Prevention of SCD in Patients With Ischemic Heart Disease Recommendations for Primary Prevention of SCD in Patients With Ischemic Heart Disease References that support the recommendations are summarized in Online Data Supplement 21. COR LOE Recommendations I A In patients with LVEF of 35% or less that is due to ischemic heart disease who are at least 40 days post-MI and at least 90 days postrevascularization, and with NYHA class II or III HF despite GDMT, an ICD is recommended if meaningful survival of greater than 1 year is expected.S7.1.2-1,S7.1.2-2 I A In patients with LVEF of 30% or less that is due to ischemic heart disease who are at least 40 days post-MI and at least 90 days postrevascularization, and with NYHA class I HF despite GDMT, an ICD is recommended if meaningful survival of greater than 1 year is Value Statement: High Value (LOE: B-R) A transvenous ICD provides high value in the primary prevention of SCD particularly when the patient s risk of death due to a VA is deemed high and the risk of nonarrhythmic death (either cardiac or noncardiac) is deemed low based on the patient s burden of comorbidities and I B-R In patients with NSVT due to prior MI, LVEF of 40% or less and inducible sustained VT or VF at electrophysiological study, an ICD is recommended if meaningful survival of greater than 1 year is expected.S7.1.2-5 CLINICAL STATEMENTS AND GUIDELINES IIa B-NR In nonhospitalized patients with NYHA class IV symptoms who are candidates for cardiac transplantation or an LVAD, an ICD is reasonable if meaningful survival of greater than 1 year is expected.S7.1.2-6 S7.1.2-9 III: No Benefit C-EO An ICD is not indicated for NYHA class IV patients with medication-refractory HF who are not also candidates for cardiac transplantation, an LVAD, or a CRT defibrillator that incorporates both pacing and defibrillation capabilities. Recommendation-Specific Supportive Text 1. The rationale for recommending that an ICD be offered to patients with NYHA class II or III HF, in addition to LVEF 35%, is based on the sur- vival benefit observed in SCD-HeFT and MADIT-II (which used LVEF cutoff of below 35% and 30%, respectively). Selection for implantation of an ICD must be individualized. Patients with serious comorbidities associated with a survival of <1 year are generally not considered ICD candidates. The recommendation to wait at least 40 days after an MI before implanting a primary prevention ICD is based on the fact that such patients were excluded from MADIT-II and SCD-HeFT and 2 other RCTs showed no survival benefit from ICDs implanted early after an acute MI.S7.1.2-10,S7.1.2-11 2. In the MADIT-II trial,S7.1.2-2 which randomized patients with LVEF 30% and prior MI to an ICD or not, approximately one third of the patients had NYHA class I symptoms. A subgroup analysis supported benefit of the ICD on survival in this 3. Economic outcomes of ICD implantation for primary prevention of SCD were assessed in 3 and SCD- which all had generally consistent results. All studies reported increased survival and life expectancy, and higher lifetime costs of medical care with an ICD than without an ICD. The incremental cost-effective- ness ratios were generally <$50000 per year of life added by an ICD, which provides high value according to the benchmarks adopted for the The value provided by an ICD was consistently high when life expectancy was projected to increase by >1.4 years.S7.1.2-18 In Figure 4. Primary prevention of SCD in patients with ischemic heart disease. Colors correspond to Class of Recommendation in Table 1. See Section 7.1.2 for discussion. *Scenarios exist for early ICD placement in select circumstances such as patients with a pacing indication or syncope Advanced HF therapy includes CRT, cardiac transplant, and LVAD thought due to VT. These are detailed elsewhere in an HRS/ACC/AHA expert consensus statement.S7.1.2-24 CRT indicates cardiac resynchronization therapy; EP, electrophysiological; GDMT, guideline-directed management and therapy; HF, heart failure; ICD, implantable cardioverter-defibrillator; IHD, ischemic heart disease; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NSVT, nonsustained ventricular tachycardia; NYHA, New York Heart Association; pts, patients; SCD, sudden cardiac death; VT, ventricular tachycardia; and WCD, wearable cardioverter-defibrillator. Recommendations for Primary Prevention of SCD in Patients With Ischemic Heart Disease (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES contrast, when survival was not increased by ICD implantation, as in the CABG-Patch trial,S7.1.2-18 the ICD did not provide value, because the higher costs were unaccompanied by a gain in life expectancy. 4. MUSTT (Multicenter Unsustained Tachycardia Trial) demonstrated that patients with prior MI, NSVT, and reduced LVEF with inducible VT at elec- trophysiological study have a higher overall mor- tality rate than similar patients without inducible Patients who received an ICD after failing to have inducible VT suppressed by an antiarrhythmic medication had lower mortal- ity rate than those who did not receive an ICD. Although the entry criteria into MUSTT required an LVEF of 40%, the average LVEF in enrolled patients was 30%, and ICD placement was not randomized but rather was selected by the treat- ing physician for patients with VT that could not be suppressed with antiarrhythmic medication therapy. MUSTT allowed enrollment of patients who were 4 days after an acute MI or revascu- larization. The ICD was of no benefit in 2 other RCTs that examined the efficacy of the ICD in the acute phase of an MI.S7.1.2-10,S7.1.2-11 In a single cen- ter observational study, an electrophysiological study was performed a median of 9 days after acute MI in 115 patients with LVEF <40% and ICDs recommended for those with inducible VT. Median follow-up was 12 months. Sustained VT was induced in 27% of patients, and 22% of those who received ICDs had spontanous VT terminated by the ICD during follow-up. None of the patients without inducible VT had VT or SCD 5. In a retrospective analysis of the UNOS (United Network for Organ Sharing) registry that extended from 1999 to 2014, data on 32599 patients showed that during a median follow-up of 154 days, 3638 patients (11%) died while on the wait- list for cardiac transplantation (9% in the ICD group versus 15% in the non-ICD group; P<0.0001). The presence of an ICD at listing was associated with an adjusted 13% relative risk reduction in mor- tality. In the subgroup of patients with an LVAD (n=9478), an ICD was associated with an adjusted 19% relative risk reduction in mortality.S7.1.2-9 In another study of 380 patients listed for heart trans- plantation between 2005 and 2009 at 1 tertiary heart transplant center, 122 patients received an ICD before or within 3 months after being listed for heart transplantation. Non-ICD patients were more likely to die while on the transplant list. In a multivariable model, the ICD was not associated with improved survival; however, that analysis was limited by the small sample size.S7.1.2-8 Another small study (n=79) conducted at 1 institution suggested that ICDs reduce the risk of SCD in patients with LVEF 30% who are awaiting heart transplanta- tion; however, this study was limited by the small number of patients.S7.1.2-6 In a retrospective mul- ticenter study of 1089 patients listed for heart transplantation, 550 patients (51%) had an ICD. In 216 patients, the ICD was for primary prevention of SCD and, in 334 patients, the ICD was for sec- ondary prevention. The remaining 539 patients did not receive an ICD. During a median time on the waiting list of 8 months, the ICD was associated with a reduction in all-cause mortality in the pri- mary and secondary prevention cohorts (estimated P=0.0001). This relationship between the ICD and improved survival persisted even after adjusting for potential confounders.S7.1.2-7 6. There are insufficient data from RCTs regard- ing the value of the ICD in patients with NYHA class IV HF. Ambulatory class IV patients with HF were included in the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial, which showed an overall improved functional status and survival with a Unless such a patient is a candidate for CRT or advanced HF therapies such as heart transplantation or an LVAD, an ICD is not expected to meaningfully prolong survival.S7.1.2-23 7.1.3. Treatment and Prevention of Recurrent VA in Patients With Ischemic Heart Disease Recommendations for Treatment of Recurrent VA in Patients With Ischemic Heart Disease References that support the recommendations are summarized in Online Data Supplements 22 and 23. COR LOE Recommendations I B-R In patients with ischemic heart disease and recurrent VA, with significant symptoms or ICD shocks despite optimal device programming and ongoing treatment with a beta blocker, amiodarone or sotalol is useful to suppress recurrent VA.S7.1.3-1 S7.1.3-3 I B-R In patients with prior MI and recurrent episodes of symptomatic sustained VT, or who present with VT storm and have failed or are intolerant of amiodarone or other antiarrhythmic medications (LOE: B-NR) S7.1.3-5 S7.1.3-9 , catheter ablation is recommended S7.1.3-10 S7.1.3-12 B-NR IIb C-LD In patients with ischemic heart disease and ICD shocks for sustained monomorphic VT or symptomatic sustained monomorphic VT that is recurrent, or hemodynamically tolerated, catheter ablation as first-line therapy may be considered to reduce recurrent VA.S7.1.3-10,S7.1.3-11 III: Harm B-R In patients with prior MI, class IC antiarrhythmic medications (eg, flecainide and propafenone) should not be used.S7.1.3-13 CLINICAL STATEMENTS AND GUIDELINES III: Harm C-LD In patients with incessant VT or VF, an ICD should not be implanted until sufficient control of the VA is achieved to prevent repeated ICD shocks.S7.1.3-14 III: No Benefit C-LD In patients with ischemic heart disease and sustained monomorphic VT, coronary revascularization alone is an ineffective therapy to prevent recurrent VT.S7.1.3-15,S7.1.3-16 Recommendation-Specific Supportive Text 1. The most common antiarrhythmic medications used for suppression of VA include amiodarone and sotalol, while mexiletine, quinidine, and ranolazine are occasionally used.S7.1.3-17,S7.1.3-18 Amiodarone appears to be more effective than sotalol and has a low rate of ventricular proarrhythmia, but has an increased risk of medication-related adverse effects that lead to its discontinuation in many patients within 18 to 24 months from initiation of therapy.S7.1.3- Data supporting effectiveness of sotalol for suppression of VA are conflicting, but given its more favorable adverse effect profile than amiodarone, it may be a better first-line antiar- rhythmic medication in appropriate patients.S7.1.3- However, sotalol is generally avoided in patients with a severely reduced LVEF <20% due to its negative inotropic effects and the risk of torsades de pointes. In a double-blind placebo- controlled study of 674 patients with HF and 10 PVCs/h and an LVEF 40% randomly assigned to receive amiodarone (336 patients) or placebo (338 patients), there was no significant difference in overall mortality or SCD between the 2 arms. There was a trend toward a reduction in overall Figure 5. Treatment of recurrent VA in patients with ischemic heart disease or NICM. Colors correspond to Class of Recommendation in Table 1. See Sections 5.6, 6, 7.1.3, and 7.2 for discussion. *Management should start with ensuring that the ICD is programmed appropriately and that potential precipitating causes, including heart failure exacerbation, are addressed. For information regarding optimal ICD programming, refer to the 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement.S7.1.3-26 APHRS indicates Asia Pacific Heart Rhythm Society; EHRA, Eu- ropean Heart Rhythm Association; HRS, Heart Rhythm Society; IHD, ischemic heart disease; ICD, implantable cardioverter-defibrillator; PVC, premature ventricular complex; NICM, nonischemic cardiomyopathy; SOLAECE, Sociedad Latinoamericana de Estimulaci n Card aca y Electrofisiolog a; VF, ventricular fibrillation; and VT, ventricular tachycardia. Recommendations for Treatment of Recurrent VA in Patients With Ischemic Heart Disease (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES mortality among the patients with NICM who received amiodarone (P=0.07).S7.1.3-20 2. Patients with prior MI may present with fre- quent episodes of sustained monomorphic VT or recurrent VF episodes that are initiated by PVCs arising from Purkinje Fibers in the peri-infarct zone. VA storms are associated with increased The arrhythmia substrate is usually in the subendocardium. The random- ized VANISH (Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) trialS7.1.3-4 compared escalating antiarrhythmic medication therapy versus catheter ablation for patients with prior MI and recurrent sustained monomorphic VT despite antiarrhythmic medications. The primary outcome, a composite of death, VT storm, or ICD shocks occurred in 59.1% in the ablation group and in 68.5% in the escalated-therapy group. There was no difference in mortality between the groups. Recurrent ICD shocks and VT storm and treatment-related adverse events were lower in the ablation group. In a subgroup analysis, patients having VT on amiodarone had better outcomes with ablation compared with increasing amiodarone or adding mexiletine to amiodarone. For patients receiving medica- tions other than amiodarone, catheter abla- tion did not reduce the risk of ICD shocks or VT storm compared with switching to amioda- rone. Although recurrent VT after catheter abla- tion is associated with increased mortality,S7.1.3-9 whether mortality is reduced by catheter abla- tion has not been established. Procedural com- plications occur in approximately 6% of patients, most of which are related to vascular access but stroke, tamponade, and atrioventricular block can occur. Procedure mortality is <1% in experi- Sustained monomorphic VT often occurs as occasional isolated episodes in patients with prior MI. Several nonrandomized studies have shown that catheter ablation reduces recurrent VT or ICD shocks.S7.1.3-5,S7.1.3-7,S7.1.3-8 A meta-anal- ysis of 5 VT ablation studiesS7.1.3-5 reported that VT recurred in 35% of patients after catheter ablation compared with 55% on antiarrhythmic medications. In a multicenter study of catheter for patients with 3 episodes of sustained VT in the prior 6 months, 53% were free from recurrent VT at 6 months follow-up; the median number of VT episodes was reduced from 11.5 to 0. Superiority of ablation over es- calating medication therapy was shown in the composite endpoint of death, VT storm, or ICD shocks by the VANISH trial.S7.1.3-4 3. Patients with prior MI who develop sustained monomorphic VT often have recurrent episodes. The VTACH (Ventricular Tachycardia Ablation in Addition to Implantable Defibrillators in Coronary Heart Disease) trialS7.1.3-11 randomized patients undergoing ICD implantation for stable sustained monomorphic VT, who had not failed antiarrhyth- mic medication therapy, to catheter ablation ver- sus ICD implantation alone. At 2 years, any VT had recurred in 53% of the ablation group and 71% of the control group. Ablation prolonged the time to recurrent VT from a median of 5.9 Several non- randomized studies have shown that catheter ablation reduces the risk of recurrent VT or ICD shocks in patients with sustained VT related to In a multicenter study of catheter ablationS7.1.3-7 for patients with 3 episodes of sustained VT in the prior 6 months, 53% were free from recurrent VT at 6 months fol- low-up; the median number of VT episodes was reduced from 11.5 to 0. A meta-analysis of 5 VT reported that VT recurred in 35% of patients after catheter ablation com- pared with 55% on antiarrhythmic medications. Another study of 63 patients with recurrent VT after MI demonstrated acute success with cath- eter ablation in 83% of mappable VTs and 40% of nonmappable VTs.S7.1.3-8 Superiority of ablation over escalating medication therapy for patients with recurrent VT despite antiarrhythmic medica- tions was shown by the VANISH trial.S7.1.3-4 See Section 5.6. demonstrated higher rates of mortal- ity or nonfatal cardiac arrest in post-MI patients treated with encainide or flecainide when used to suppress PVCs and NSVT.S7.1.3-13 Propafenone is associated with increased mortality in SCA survi- vors compared with beta blockers, amiodarone, and the ICD.S7.1.3-22 5. Implantation of an ICD prior to achieving sup- pression of frequent or incessant VA places the patient at high risk of repetitive shocks, which can be psychologically detrimental and has been asso- ciated with increased mortality.S7.1.3-23,S7.1.3-24 6. Sustained monomorphic VT in the setting of prior MI is typically due to scar-related reentry and is not due to acute ischemia. Although it may be appropriate to recommend revascular- ization when another indication for revascular- ization exists, revascularization alone is unlikely to reduce the recurrence of monomorphic VT and specific therapies such as antiarrhythmic medications or ablation may be needed to pre- On the contrary, revascu- larization might be beneficial in patients with CLINICAL STATEMENTS AND GUIDELINES ischemic heart disease and VF, polymorphic VT, or exercise-induced arrhythmias associated with 7.2. Nonischemic Cardiomyopathy Recommendations for Patients With NICM References that support the recommendations are summarized in Online Data Supplement 24. COR LOE Recommendations I B-NR In patients with suspected NICM from myocardial infiltrative processes, cardiac MRI with late gadolinium enhancement is useful for IIa B-NR In patients with suspected NICM, cardiac MRI with late gadolinium enhancement can be useful for assessing risk of SCA/SCD.S7.2-1 S7.2-3 IIa C-EO In patients with NICM who develop conduction disease or LV dysfunction at less than 40 years of age, or who have a family history of NICM or SCD in a first-degree relative (<50 years of age), genetic counseling and genetic testing are reasonable to detect a heritable disease that may clarify prognosis and facilitate cascade screening of relatives.S7.2-4,S7.2-5 Recommendation-Specific Supportive Text 1. Cardiac MRI allows for evaluation of structural heart disease and assessment of LV and RV func- tion including quantification of LVEF, LV mass and volume, and valvular structure. Cardiac MRI can help in the evaluation for myocardial infil- trative processes and evidence of scar, indicated by delayed hyperenhancement, associated with 2. The presence of delayed hyperenhancement has been associated with worse outcomes, including 3. It is important to consider genetic etiologies for NICM. Goals of genetic testing for NICM are to identify at-risk relatives who host a disease- causing mutation and to help clarify prognosis. Lamin A/C and NKX 2.5 mutationsS7.2-7 S7.2-12 are associated with a particularly high risk of early conduction disease, arrhythmias, and SCD, and their identification often prompts consideration of early use of an ICD. It is unknown, however, whether early pharmacological treatment of mutation-positive, asymptomatic subjects can prevent or delay manifestation of the disease or whether genetic testing ultimately improves survival. 7.2.1. Secondary Prevention of SCD in Patients With NICM Recommendations for Secondary Prevention of SCD in Patients With NICM References that support the recommendations are summarized in Online Data Supplements 25 and 26. COR LOE Recommendations I B-R In patients with NICM who either survive SCA due to VT/VF or experience hemodynamically unstable VT (LOE: B-R) S7.2.1-1 S7.2.1-4 or stable sustained VT (LOE: B-NR) S7.2.1-5 not due to reversible causes, an ICD is recommended if meaningful survival greater than 1 year is expected. B-NR IIa B-NR In patients with NICM who experience syncope presumed to be due to VA and who do not meet indications for a primary prevention ICD, an ICD or an electrophysiological study for risk stratification for SCD can be beneficial if meaningful survival greater than 1 year is IIb B-R In patients with NICM who survive a cardiac arrest, have sustained VT, or have symptomatic VA who are ineligible for an ICD (due to a limited life-expectancy and/ or functional status or lack of access to an ICD), amiodarone may be considered for prevention of SCD.S7.2.1-12,S7.2.1-13 Recommendation-Specific Supportive Text 1. Three prospective RCTs compared the ICD with pharmacological therapy in patients resuscitated from SCA due to VT/VF or hemodynamically sig- The antiarrhythmic medications most commonly used were amio- darone, a beta blocker, or both, although in the CASH (Cardiac Arrest Study Hamburg) trial,S7.2.1-4 there was also a propafenone arm that was termi- nated early due to increased mortality. The 3 tri- als enrolled 1963 patients, but only 292 (14.8%) had NICM. A meta-analysis in which data from AVID and CIDS were pooled found a nonsignifi- cant 31% reduction in all-cause mortality relative to medical therapy in patients with NICM.S7.2.1-3 Although this analysis was underpowered, the observed mortality reduction was consistent with the observed benefit in the entire study popula- tion. In the AVID trial,S7.2.1-1 patients who were ineligible for the RCT were included in a registry, and sustained VT without serious symptoms or hemodynamic compromise was associated with a mortality rate similar to that of patients with unstable VT who were assigned to medical ther- apy. Therefore, stable VT is likely a marker for a substrate capable of producing subsequent lethal CLINICAL STATEMENTS AND GUIDELINES 2. Small observational studies demonstrated high mortality and frequent appropriate ICD shocks in patients with syncope and NICM.S7.2.1-7 S7.2.1-9 The assumption that malignant VAs are the likely cause of syncope and that the ICD would be protec- tive has recently been challenged. In a subgroup analysis of SCD-HeFT that included 472 patients, the ICD did not reduce either recurrent syncope or the increased risk of mortality associated A subgroup analysis of the MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy) trial found syncope to be arrhythmic only in 39% These studies suggest that syncope in some HF patients may be an indica- tor of an end-stage cardiomyopathy associated with a poor prognosis.S7.2.1-11 In a substudy of DEFINITE, inducible sustained VT/VF was found in a minority of patients, but it was associated with appropriate ICD therapy.S7.2.1-14 Another study of electrophysiological testing in NICM found inducible VT/VF in 27.8% of patients, which was associated with future ICD events.S7.2.1-15 In a study of patients with NICM, cardiac mortality correlated with LVEF but not with inducibility on Based on these data, many experts are uncomfortable withhold- ing an ICD from patients with NICM who expe- rience syncope potentially due to a VA even if the electrophysiological study shows no inducible sustained VT. 3. Access to ICDs may be limited by financial, medi- cal, or personal considerations. In addition, not all patients at high risk of SCD meet ICD indica- tions, such as those with class IV HF without CRT possibility or with a life expectancy <1 year. A meta-analysis of RCTs, which examined the use of amiodarone for the prevention of SCD, included 15 studies with 8522 patients assigned to amio- darone or placebo/control.S7.2.1-12 Amiodarone reduced the risk of SCD by 29%; however, it did not reduce all-cause mortality and was asso- ciated with an increased risk of pulmonary and thyroid toxicity. In a subgroup analysis, the ben- efit of amiodarone appeared similar in patients with ischemic cardiomyopathy and those with In a separate meta-analysis,S7.2.1-13 the evidence was insufficent to support amioda- rone s efficacy for reduction of SCD and all-cause mortality in survivors of cardiac arrest or those with syncope due to VA. A subgroup analysis of the VALIANT (Valsartan in Acute Myocardial Infarction) trial found that amiodarone was asso- ciated with increased mortality in patients with NYHA class III HF.S7.2.1-17 These data call for a care- ful and nuanced approach to using amiodarone for the secondary prevention of SCD in patients with NICM. 7.2.2. Primary Prevention of SCD in Patients With NICM Recommendations for Primary Prevention of SCD in Patients With NICM References that support the recommendations are summarized in Online Data Supplements 27 and 28. COR LOE Recommendations I A In patients with NICM, HF with NYHA class II III symptoms and an LVEF of 35% or less, despite GDMT, an ICD is recommended if meaningful survival of greater than 1 year is IIa B-NR In patients with NICM due to a Lamin A/C mutation who have 2 or more risk factors (NSVT, LVEF <45%, nonmissense mutation, and male sex), an ICD can be beneficial if meaningful survival of greater than 1 year is IIb B-R In patients with NICM, HF with NYHA class I symptoms and an LVEF of 35% or less, despite GDMT, an ICD may be considered if meaningful survival of greater than 1 year is III: No Benefit C-EO In patients with medication-refractory NYHA class IV HF who are not also candidates for cardiac transplantation, an LVAD, or a CRT defibrillator that incorporates both pacing and defibrillation capabilities, an ICD should not be implanted. Recommendation-Specific Supportive Text 1. For all patients with NICM, it is imperative that patients be on GDMT for HF for at least 3 months before a primary prevention ICD is offered. Four initially evaluated ICDs for primary prevention of SCD in patients with NICM. TwoS7.2.2-2,S7.2.2-6 were small studies that were terminated early due to a low event rate. In DEFINITE,S7.2.2-5 an ICD reduced the risk of SCD, with a trend toward reduced all- cause mortality. SCD-HeFT included 792 NICM Total mortality at 5 years was 27% in the placebo group and 21% in the ICD group (P=0.06). A pooled analysis of these studies dem- onstrated a significant 31% reduction in all-cause mortality for ICD relative to medical therapy.S7.2.2-4 The DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality) trialS7.2.2-11 raised ques- tions about the role of primary pevention ICDs in patients with NICM. This trial randomized 1116 patients with NICM LVEF <35% and class II, III, or IV (if CRT was planned) HF to an ICD or no ICD. CRT (either ICD or pacemaker) was pres- ent in 58% of patients in the ICD and medical CLINICAL STATEMENTS AND GUIDELINES therapy arms. Therefore, the results of DANISH should not be generalized to patients with NICM who are ineligible for CRT. During a median follow-up of 5.6 years, ICD reduced SCD from 8.4% to 4.3%, but there was no difference in Several meta-analyses have been published.S7.2.2-12,S7.2.2-13 One provided data on ICDs with and without CRT and showed survival benefit from the ICD.S7.2.2-13 The second used patient level data from 2 trials and adopted a more robust approach to reducing heterogene- ity by excluding patients with CRT and those ran- domized to antiarrhythmic medications; a 25% relative risk reduction in mortality with an ICD 2. Laminopathies are diseases caused by mutations mainly in the Lamin A/C gene that produce various inherited diseases including subtypes of muscular dystrophy and progeria. Isolated cardiac involve- ment is also observed and is an important cause of familial cardiomyopathy.S7.2.2-9 The disease is highly penetrant such that all affected individu- als have evidence of disease by 60 years of age. Cardiac manifestations may include atrial fibril- lation, conduction disturbances, VA, and NICM. A number of observational studies reported a high risk of SCD when cardiac involvement is One study reported SCD as the most frequent mode of death (46%) in both the isolated cardiac and the neuromuscular phe- notypes of Lamin diseases.S7.2.2-9 In a cohort of 269 LMNA mutation positive individuals,S7.2.2-10 NSVT during ambulatory electrocardiographic monitor- ing, LVEF <45% at first evaluation, male sex, and nonmissense mutations were independent risk factors for VA. Malignant VA were observed only in persons with 2 of these risk factors.S7.2.2-10 No studies have tested the effect of the ICD on long- term survival. 3. Patients with NICM and class I HF symptoms were not included in SCD-HeFT or DANISH.S7.2.2-1,S7.2.2-11 Although such patients were included in the DEFINITE trial, only 99 (21.6%) of 458 patients in the DEFINITE trial had class I HF.S7.2.2-5 Therefore, it is uncertain whether a primary prevention ICD in such patients improves survival. 4. There are insufficient data from RCTs regarding the value of the ICD in patients with NYHA class IV. Ambulatory class IV HF patients were included in the COMPANION trial that, overall, showed improved functional status and survival with a Unless such a patient is a candidate for CRT or advanced HF therapies such as heart transplantation or an LVAD, an ICD is not expected to meaningfully prolong survival.S7.2.2-3 7.2.3. Treatment of Recurrent VA in Patients With NICM Recommendations for Treatment of Recurrent VA in Patients With NICM References that support the recommendations are summarized in Online Data Supplement 29. COR LOE Recommendations IIa B-R In patients with NICM and an ICD who experience spontaneous VA or recurrent appropriate shocks despite optimal device programming and treatment with a beta blocker, amiodarone or sotalol can be IIa B-NR In patients with NICM and recurrent sustained monomorphic VT who fail or are intolerant of antiarrhythmic medications, catheter ablation can be useful for reducing recurrent VT and ICD Recommendation-Specific Supportive Text 1. ICDs reduce mortality from VA, yet ICD shocks are painful and associated with significant morbidity and poor QoL. Although ICDs are highly programmable and provide antitachy- cardia pacing therapy that can terminate most VT episodes without the need for a shock, pre- vention of shocks, both appropriate and inap- propriate, remains an important concern. In the OPTIC (Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients) study, 412 patients with documented VT and VF who received an ICD within 21 days of the docu- were randomized to amiodarone plus beta blocker, sotalol alone, or beta blocker alone. Over 1 year, shocks occurred in 38.5% assigned to beta blocker alone, 24.3% assigned to sotalol, and 10.3% assigned to amiodarone plus beta blocker. The rates of study medication discontinuation at 1 year were 18.2% for amiodarone, 23.5% for sotalol, and 5.3% for beta blocker alone. Adverse pulmonary and thyroid events and symptomatic bradycar- dia were more common among patients ran- domized to amiodarone. Thus, amiodarone plus beta blocker were more effective than sotalol in preventing ICD shocks but at the expense of increased risk of medication-related adverse Sotalol should not be used in patients with an LVEF <20% due to its negative inotropic effects. 2. Sustained monomorphic VT due to NICM is most often due to scar-related reentry. Cardiac MRI often indicates scar location, which tends to be basal along the mitral annulus or in the The VT substrate can be CLINICAL STATEMENTS AND GUIDELINES Figure 6. Secondary and primary prevention of SCD in patients with NICM. Colors correspond to Class of Recommendation in Table 1. See Section 7.2 for discussion. *ICD candidacy as determined by functional status, life expectancy or patient preference. 2 indicates secondary; EP, electrophysiological; GDMT, guideline-directed management and therapy; HF, heart failure; ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; NICM, nonischemic cardiomyopathy; SCA, sudden cardiac arrest; SCD, sudden cardiac death; VA, ventricular arrhythmia; and WCD, wearable cardioverter-defibrillator. subendocardial, subepicardial, or intramyo- cardial, and all locations may be affected and require endocardial and epicardial ablation. In the HELP-VT (Heart Center of Leipzig VT) successful ablation of all VT mor- phologies was achieved in 66.7% of patients with NICM, compared with the 77.4% suc- cess rate in ischemic cardiomyopathy. An epi- cardial approach to ablation was required in 30.2% of NICM patients, compared with only 1.2% with ischemic cardiomyopathy. Epicardial ablation was an independent predictor of suc- cessful ablation. Acute and long-term success of ablation is lower for NICM, compared with post-MI patients. The long-term survival-free of VT recurrence after catheter ablation appears to be better for patients with ischemic than Risks are similar to those observed for post-MI VT ablation, with additional risks of epicardial access and ablation when required. Although any NICM can produce scar-related VT, cardiac sarcoidosis (see Section 7.6) and Lamin muta- tions are particularly associated with sustained 7.3. Arrhythmogenic Right Ventricular Cardiomyopathy Recommendations for Arrhythmogenic Right Ventricular Cardiomyopathy References that support the recommendations are summarized in Online Data Supplement 30. COR LOE Recommendations I B-NR In selected first-degree relatives of patients with arrhythmogenic right ventricular cardiomyopathy, clinical screening for the disease is recommended along with genetic counseling and genetic testing, if the proband has a disease causing mutation.S7.3-1 S7.3-4 I B-NR In patients with suspected arrhythmogenic right ventricular cardiomyopathy and VA or electrocardiographic abnormalities, cardiac MRI is useful for establishing a diagnosis and for risk stratification.S7.3-5 S7.3-8 I B-NR In patients with arrhythmogenic right ventricular cardiomyopathy and an additional marker of increased risk of SCD (resuscitated SCA, sustained VT, significant ventricular dysfunction with RVEF or LVEF 35%), an ICD is recommended if meaningful survival greater than 1 year is I B-NR In patients with arrhythmogenic right ventricular cardiomyopathy and VA, a beta blocker is recommended.S7.3-11,S7.3-14,S7.3-15 CLINICAL STATEMENTS AND GUIDELINES I B-NR In patients with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy, avoiding intensive exercise is IIa B-NR In patients with clinically diagnosed or suspected arrhythmogenic right ventricular cardiomyopathy, genetic counseling and genetic testing can be useful for diagnosis and for gene-specific targeted family IIa B-NR In patients with arrhythmogenic right ventricular cardiomyopathy and syncope presumed due to VA, an ICD can be useful if meaningful survival greater than 1 year is IIa B-NR In patients with clinical evidence of arrhythmogenic right ventricular cardiomyopathy but not VA, a beta blocker can be useful.S7.3-14,S7.3-15 IIa B-NR In patients with arrhythmogenic right ventricular cardiomyopathy and recurrent symptomatic sustained VT in whom a beta blocker is ineffective or not tolerated, catheter ablation with availability of a combined endocardial/epicardial approach can be beneficial.S7.3-27 S7.3-33 IIa B-NR In patients with suspected arrhythmogenic right ventricular cardiomyopathy, a signal averaged ECG can be useful for diagnosis and risk stratification.S7.3-14,S7.3-34,S7.3-35 IIb B-NR In asymptomatic patients with clinical evidence of arrhythmogenic right ventricular cardiomyopathy, an electrophysiological study may be considered for risk Synopsis Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy that predominantly af- fects the right ventricle but can affect the left ven- tricle causing areas of myocardial replacement with fibrosis and adipose tissue that frequently causes VA and SCD. Recommendation-Specific Supportive Text 1. Selected first-degree relatives refers to rela- tives who are willing to undergo further testing and who could benefit from further screening and testing (and not the terminally ill patients or those who do not want to be screened and tested). 