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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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).


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.


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.


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.


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.


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.


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). Arrhythmogenic right ventricular cardio- myopathy is often due to a mutation involving a desmosomal protein, and it usually has auto- somal dominant inheritance with variable pen- etrance. SCD can be the initial manifestation of arrhythmogenic right ventricular cardiomyopathy. Clinical screening with ECG, cardiac imaging, and ambulatory rhythm monitoring and/or exer- cise testing may identify family members at risk for arrhythmogenic right ventricular cardiomy- opathy. Arrhythmogenic right ventricular cardio- myopathy is detected clinically in approximately most commonly in siblings or symptomatic first- When a proband is identi- fied with a disease-causing mutation, targeted genotype screening can identify mutation positive with approximately 35% of muta- tion positive individuals ultimately developing progressive disease expression.S7.3-1,S7.3-4 In stud- ies of arrhythmogenic right ventricular cardiomy- opathy mutation-positive individuals who do not initially manifest the disease, 8% to 16% have a major arrhythmic event over the next 7 to 39 Early identification of affected or potentially affected family members can allow lifestyle modifications in sports participation and serial monitoring for development of electrocar- diographic abnormalities, symptoms, ventricular dysfunction, or arrhythmia. As genetic testing for arrhythmogenic right ventricular cardiomyopathy has subtle complexities, the decision to proceed with family screening is facilitated by informed genetic counseling to discuss the cost of test- ing, the potential lack of a single gene as the determinant for disease expression, psychological implications of uncertain disease progression, and implications for lifestyle modification, screening, and potential treatment. 2.


As genetic testing for arrhythmogenic right ventricular cardiomyopathy has subtle complexities, the decision to proceed with family screening is facilitated by informed genetic counseling to discuss the cost of test- ing, the potential lack of a single gene as the determinant for disease expression, psychological implications of uncertain disease progression, and implications for lifestyle modification, screening, and potential treatment. 2. Cardiac MRI provides high-quality assess- ment of ventricular function, size, regional wall motion abnormalities, and extent of scar and fibrosis (late gadolinium enhancement) that are seen in 30% to 95% of patients with the clini- cal diagnosis of arrhythmogenic right ventricu- Cardiac MRI detects biventricular involvement in 34% to 56% of patients, with isolated LV involve- ment noted in 4% to 9% of patients.S7.3-37 S7.3-40 Cardiac MRI should include assessment of late gadolinium enhancement with quantification of fibrosis. Application of the 2010 Task Force Criteria to cardiac MRI criteria for diagnosis of arrhythmogenic right ventricular cardiomyopa- thy has improved the specificity of this test.S7.3- Electrocardiographic and Holter findings precede detectable cardiac MRI abnormalities in arrhythmogenic right ventricular cardiomyopa- thy mutation-positive individuals, with only 4% of patients with normal electrocardiographic and Holter results having cardiac MRI abnormalities, Recommendations for Arrhythmogenic Right Ventricular Cardiomyopathy (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES suggesting that evaluation of cardiac structure and function using cardiac MRI may be unnecessary in mutation-positive individuals who do not have The presence of both electrocardiographic abnormalities and abnor- mal cardiac MRI findings may identify patients at an increased risk for developing sustained Areas of scar identified on cardiac MRI have correlated with the location of VT sub- strate identified by endocardial and epicardial During early stages of disease, a baseline cardiac MRI may provide useful informa- tion along with electrocardiographic and rhythm abnormalities to monitor disease progression over time.


Application of the 2010 Task Force Criteria to cardiac MRI criteria for diagnosis of arrhythmogenic right ventricular cardiomyopa- thy has improved the specificity of this test.S7.3- Electrocardiographic and Holter findings precede detectable cardiac MRI abnormalities in arrhythmogenic right ventricular cardiomyopa- thy mutation-positive individuals, with only 4% of patients with normal electrocardiographic and Holter results having cardiac MRI abnormalities, Recommendations for Arrhythmogenic Right Ventricular Cardiomyopathy (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES suggesting that evaluation of cardiac structure and function using cardiac MRI may be unnecessary in mutation-positive individuals who do not have The presence of both electrocardiographic abnormalities and abnor- mal cardiac MRI findings may identify patients at an increased risk for developing sustained Areas of scar identified on cardiac MRI have correlated with the location of VT sub- strate identified by endocardial and epicardial During early stages of disease, a baseline cardiac MRI may provide useful informa- tion along with electrocardiographic and rhythm abnormalities to monitor disease progression over time. Experience and expertise in interpretation of cardiac MRI are important.S7.3-5,S7.3-8 3. Arrhythmogenic right ventricular cardiomy- opathy is characterized by progressive ven- tricular myocyte loss with replacement by fatty or fibrous tissue, and is associated with progressive ventricular dysfunction that may involve both ventricles.


Arrhythmogenic right ventricular cardiomy- opathy is characterized by progressive ven- tricular myocyte loss with replacement by fatty or fibrous tissue, and is associated with progressive ventricular dysfunction that may involve both ventricles. VA, syncope, and SCD may occur at a relatively young age, particularly in the second and third decades of life and often occurring during physical Sustained VT is an important predictor of SCA and SCD or appropri- ate ICD shocks in patients with arrhythmogenic right ventricular cardiomyopathy.S7.3-10,S7.3-13 In patients receiving an ICD for primary prevention, appropriate ICD shocks are reported in 24% to As sustained VT in arrhythmogenic right ventricular cardiomy- opathy patients is monomorphic in 55% to 90% of episodes based on ICD interrogation or elec- antitachycardia pacing algorithms are used to terminate VT. 4. Frequent PVCs, >760 to 1000 per 24 hours dur- ing ambulatory rhythm monitoring, correlate with The presence of NSVT or sustained VT is an important predictor of adverse The increased arrhythmia risk conferred by intense exercise is consistent with beta-adrenergic modu- lation of disease expression.S7.3-17,S7.3-20,S7.3-21 An observational registry reported that treatment with atenolol or amiodarone was associated with less clinically relevant VA, while sotalol was associ- ated with no effect or increased arrhythmia.S7.3-15 Ambulatory monitoring to assess VA burden and adequacy of beta-blocker therapy is usually 5.


Frequent PVCs, >760 to 1000 per 24 hours dur- ing ambulatory rhythm monitoring, correlate with The presence of NSVT or sustained VT is an important predictor of adverse The increased arrhythmia risk conferred by intense exercise is consistent with beta-adrenergic modu- lation of disease expression.S7.3-17,S7.3-20,S7.3-21 An observational registry reported that treatment with atenolol or amiodarone was associated with less clinically relevant VA, while sotalol was associ- ated with no effect or increased arrhythmia.S7.3-15 Ambulatory monitoring to assess VA burden and adequacy of beta-blocker therapy is usually 5. Patients with arrhythmogenic right ventricular cardiomyopathy have a significantly increased risk of SCD during exertion.S7.3-16,S7.3-17,S7.3-20,S7.3-21 Vigorous exercise in patients with arrhythmogenic right ventricular cardiomyopathy has been shown to impair myocardial function by echocardiogra- phy and cardiac MRI.S7.3-19 Participation in high intensity/duration or endurance physical activity accelerates the penetrance/disease progression and arrhythmic risk for arrhythmogenic right ventricular cardiomyopathy patients and muta- tion positive individuals, as well as mutation positive family members.S7.3-17,S7.3-19 S7.3-21 Patients with arrhythmogenic right ventricular cardiomy- opathy who participate in competitive sports are at increased risk for VT or SCD, compared with those who participate in recreational sports or Exercise influences disease progression in a linear manner; family members who limited activity to less than the AHA recommended minimum for activity guide- lines (<650 metabolic equivalent hours per year [MET-Hr/year]) were less likely to develop VA or In a study of arrhyth- mogenic right ventricular cardiomyopathy pro- bands and exercise, athletes (defined as subjects with 4h vigorous exercise/week) were found to have reduced biventricular function compared with nonathletes in arrhythmogenic right ven- tricular cardiomyopathy patients and in muta- tion-positive family members.S7.3-19 Many advise limiting exercise intensity and duration to <650 6.


Patients with arrhythmogenic right ventricular cardiomyopathy have a significantly increased risk of SCD during exertion.S7.3-16,S7.3-17,S7.3-20,S7.3-21 Vigorous exercise in patients with arrhythmogenic right ventricular cardiomyopathy has been shown to impair myocardial function by echocardiogra- phy and cardiac MRI.S7.3-19 Participation in high intensity/duration or endurance physical activity accelerates the penetrance/disease progression and arrhythmic risk for arrhythmogenic right ventricular cardiomyopathy patients and muta- tion positive individuals, as well as mutation positive family members.S7.3-17,S7.3-19 S7.3-21 Patients with arrhythmogenic right ventricular cardiomy- opathy who participate in competitive sports are at increased risk for VT or SCD, compared with those who participate in recreational sports or Exercise influences disease progression in a linear manner; family members who limited activity to less than the AHA recommended minimum for activity guide- lines (<650 metabolic equivalent hours per year [MET-Hr/year]) were less likely to develop VA or In a study of arrhyth- mogenic right ventricular cardiomyopathy pro- bands and exercise, athletes (defined as subjects with 4h vigorous exercise/week) were found to have reduced biventricular function compared with nonathletes in arrhythmogenic right ven- tricular cardiomyopathy patients and in muta- tion-positive family members.S7.3-19 Many advise limiting exercise intensity and duration to <650 6. The proband with arrhythmogenic right ven- tricular cardiomyopathy is usually diagnosed by the presence of clinical symptoms along with the presence of arrhythmogenic right ventricu- lar cardiomyopathy Task Force criteria including: abnormalities on ECG, structural and functional changes of either ventricle, arrhythmias, and arrhythmogenic right ventricular cardiomyopathy in first-degree relatives.S7.3-6 A pathogenic genetic mutation was added to the major Task Force criteria in 2010.S7.3-44 The yield of genetic test- ing in probands with suspected arrhythmogenic right ventricular cardiomyopathy is generally 30% to 54%, and is up to 58% among patients with a strong family history of SCD in multiple A negative genetic test for arrhythmogenic right ventricular cardiomyop- athy does not exclude the disease, and a positive genetic test currently does not guide therapy.S7.3-22 For the proband with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy, identification of pathogenic mutations provides limited prognostic information relative to the risk or development of HF.S7.3-22 In a large multicenter study, the presence of posi- tive mutations among probands was not asso- ciated with a difference in mortality or cardiac CLINICAL STATEMENTS AND GUIDELINES However, the identification of a pathogenic mutation facilitates targeted genetic screening for that mutation in first- degree relatives, that may identify approximately highest among siblings, and those with symptoms.S7.3-4 Screening for the specific mutation can identify some gene positive family members prior to disease expres- sion, while relieving others from the need for life- style changes and long-term monitoring.S7.3-2,S7.3-3 7.


The proband with arrhythmogenic right ven- tricular cardiomyopathy is usually diagnosed by the presence of clinical symptoms along with the presence of arrhythmogenic right ventricu- lar cardiomyopathy Task Force criteria including: abnormalities on ECG, structural and functional changes of either ventricle, arrhythmias, and arrhythmogenic right ventricular cardiomyopathy in first-degree relatives.S7.3-6 A pathogenic genetic mutation was added to the major Task Force criteria in 2010.S7.3-44 The yield of genetic test- ing in probands with suspected arrhythmogenic right ventricular cardiomyopathy is generally 30% to 54%, and is up to 58% among patients with a strong family history of SCD in multiple A negative genetic test for arrhythmogenic right ventricular cardiomyop- athy does not exclude the disease, and a positive genetic test currently does not guide therapy.S7.3-22 For the proband with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy, identification of pathogenic mutations provides limited prognostic information relative to the risk or development of HF.S7.3-22 In a large multicenter study, the presence of posi- tive mutations among probands was not asso- ciated with a difference in mortality or cardiac CLINICAL STATEMENTS AND GUIDELINES However, the identification of a pathogenic mutation facilitates targeted genetic screening for that mutation in first- degree relatives, that may identify approximately highest among siblings, and those with symptoms.S7.3-4 Screening for the specific mutation can identify some gene positive family members prior to disease expres- sion, while relieving others from the need for life- style changes and long-term monitoring.S7.3-2,S7.3-3 7. Syncope is reported in 16% to 39% of arrhythmo- genic right ventricular cardiomyopathy patients at the time of diagnosis,S7.3-13,S7.3-14,S7.3-16,S7.3-41,S7.3-43 is frequently exercise-related, and has been associated with high arrhythmic risk in some Among patients with arrhyth- mogenic right ventricular cardiomyopathy and implanted ICDs, syncope was an important pre- dictor of appropriate shocks in 1 study,S7.3-10 but not in other studies.S7.3-9,S7.3-12,S7.3-13,S7.3-43 Studies have not provided information about ventricular function or abnormalities on ECG in patients with syncope, limiting its assessment as an indepen- dent risk factor.


Syncope is reported in 16% to 39% of arrhythmo- genic right ventricular cardiomyopathy patients at the time of diagnosis,S7.3-13,S7.3-14,S7.3-16,S7.3-41,S7.3-43 is frequently exercise-related, and has been associated with high arrhythmic risk in some Among patients with arrhyth- mogenic right ventricular cardiomyopathy and implanted ICDs, syncope was an important pre- dictor of appropriate shocks in 1 study,S7.3-10 but not in other studies.S7.3-9,S7.3-12,S7.3-13,S7.3-43 Studies have not provided information about ventricular function or abnormalities on ECG in patients with syncope, limiting its assessment as an indepen- dent risk factor. Syncope may be a harbinger of progression of underlying disease and should be integrated into the decision-making process for ICD implantation with the patient. 8. Asymptomatic patients with arrhythmogenic right ventricular cardiomyopathy and no VA or ventric- ular dysfunction are generally observed without antiarrhythmic therapy other than beta-blocker therapy, with ongoing periodic reassessment for the development of arrhythmias or ventricular Atenolol was shown to reduce VA in 1 study.S7.3-15 Ambulatory monitor- ing and/or exercise testing can be performed to assess adequacy of beta-blocking dosing. 9. Interrogation of ICDs shows that >90% of sponta- neous sustained VTs in arrhythmogenic right ven- tricular cardiomyopathy are monomorphic,S7.3-12 while sustained monomorphic VT is induc- ible at electrophysiological study in 55% of VT is usually related to scar-related reentry, and the subepicardium usually has more extensive scar than the endocardium.S7.3-27 In experienced centers, use of epicardial map- ping and ablation is associated with better Important complications including pericardial tamponade, MI, and death occur in 2.3% to 3.3% of abla- emphasizing the need for performance in centers with specialized expertise in epicardial procedures. Ablation reduces the fre- quency of recurrent VT, although 27% to 55% have at least 1 recurrence; ablation of VT in arrhythmogenic right ventricular cardiomyopathy patients does not eliminate the need for an ICD in appropriate candidates.


Ablation reduces the fre- quency of recurrent VT, although 27% to 55% have at least 1 recurrence; ablation of VT in arrhythmogenic right ventricular cardiomyopathy patients does not eliminate the need for an ICD in appropriate candidates. The potential risk of VT recurrence due to disease pro- gression should be reviewed with patients when considering ablation. There are no randomized comparisons of antiarrhythmic therapy to sup- press recurrent VT. Beta blockers, sotalol and ami- odarone have been used.S7.3-15 In an observational series, sotalol suppressed inducible VT in 58% of patients with <10% of patients experienc- ing arrhythmia recurrence during follow-up.S7.3-48 Effectiveness of the different medications appears to be variable, and so more studies are needed. 10. In arrhythmogenic right ventricular cardiomyop- athy, areas of fibrofatty scar in the RV free wall create areas of delayed ventricular activation causing fractionated deflections following the QRS, known as epsilon waves on the surface ECG (a major criterion) and late potentials in the signal averaged ECG (minor criterion) in the 2010 Task Force Criteria for diagnosis of arrhythmogenic right ventricular cardiomyopathy.S7.3-6 When the standard ECG QRS duration is 110 ms, criteria for abnormal signal-averaged ECG include any 1 of the following: filtered QRS duration 114 ms, duration of the terminal QRS <40 uV exceeding 37 ms, or a root mean square voltage in the terminal Abnormal findings on sig- nal averaged ECG correlated with disease severity on cardiac MRI,S7.3-35 and increased adverse events In an assessment of the diagnostic use of testing for arrhythmogenic right ventricu- lar cardiomyopathy, signal averaged ECG was of greater value than cardiac MRI or biopsy.S7.3-14 11. The value of an electrophysiological study is uncer- tain in asymptomatic arrhythmogenic right ven- tricular cardiomyopathy patients with preserved ventricular function in predicting subsequent risk for SCD.


The value of an electrophysiological study is uncer- tain in asymptomatic arrhythmogenic right ven- tricular cardiomyopathy patients with preserved ventricular function in predicting subsequent risk for SCD. Studies of programmed ventricular stimulation in patients with definite or probable arrhythmogenic right ventricular cardiomyopathy include most symptomatic patients, making rec- ommendations on asymptomatic patients difficult. Electrophysiological studies induce sustained VT in ; many of whom have had prior spontaneous episodes of sustained VT. In patients with primary prevention ICDs, inducible sustained VT did not predict sub- sequent appropriate ICD shocks.S7.3-13 In 1 study including symptomatic patients, patients without inducible VT were less likely to receive appropriate In asymptomatic patients without evidence of VA on ambulatory monitoring, a neg- ative electrophysiological study may have limited value in decision-making for an ICD. CLINICAL STATEMENTS AND GUIDELINES 7.4. Hypertrophic Cardiomyopathy Recommendations for HCM References that support the recommendations are summarized in Online Data Supplement 31. COR LOE Recommendations I B-NR In patients with HCM, SCD risk stratification should be performed at the time of initial evaluation and periodically I B-NR In patients with HCM who have survived an SCA due to VT or VF, or have spontaneous sustained VT causing syncope or hemodynamic compromise, an ICD is recommended if meaningful survival greater than 1 year is expected.S7.4-1,S7.4-6,S7.4-9,S7.4-10 I B-NR In first-degree relatives of patients with HCM, an ECG and echocardiogram should be I B-NR In first-degree relatives of patients with HCM due to a known causative mutation, genetic counseling and mutation-specific genetic testing are IIa B-NR In patients with clinically suspected or diagnosed HCM, genetic counseling and genetic testing IIa B-NR In patients with HCM and 1 or more of the following risk factors, an ICD is reasonable if meaningful survival of greater than 1 year is expected: a.


COR LOE Recommendations I B-NR In patients with HCM, SCD risk stratification should be performed at the time of initial evaluation and periodically I B-NR In patients with HCM who have survived an SCA due to VT or VF, or have spontaneous sustained VT causing syncope or hemodynamic compromise, an ICD is recommended if meaningful survival greater than 1 year is expected.S7.4-1,S7.4-6,S7.4-9,S7.4-10 I B-NR In first-degree relatives of patients with HCM, an ECG and echocardiogram should be I B-NR In first-degree relatives of patients with HCM due to a known causative mutation, genetic counseling and mutation-specific genetic testing are IIa B-NR In patients with clinically suspected or diagnosed HCM, genetic counseling and genetic testing IIa B-NR In patients with HCM and 1 or more of the following risk factors, an ICD is reasonable if meaningful survival of greater than 1 year is expected: a. Maximum LV wall thickness 30 mm b. SCD in 1 or more first-degree relatives presumably caused by HCM c. 1 or more episodes of unexplained syncope within the preceding 6 months C-LD C-LD IIa B-NR In patients with HCM who have spontaneous NSVT (LOE: C-LD) S7.4-2,S7.4-26,S7.4-27 or an abnormal blood pressure response with exercise (LOE: B-NR) S7.4-5,S7.4-28,S7.4-29 , who also have additional SCD risk modifiers or high-risk features, an ICD is reasonable if meaningful survival greater than 1 year is expected. C-LD IIb B-NR In patients with HCM who have NSVT or an abnormal blood pressure response with exercise (LOE: but do not have any other SCD risk modifiers, an ICD may be considered, but its benefit is uncertain.


C-LD IIb B-NR In patients with HCM who have NSVT or an abnormal blood pressure response with exercise (LOE: but do not have any other SCD risk modifiers, an ICD may be considered, but its benefit is uncertain. B-NR IIb C-LD In patients with HCM and a history of sustained VT or VF, amiodarone may be considered when an ICD is not feasible or not preferred by the patient.S7.4-30,S7.4-31 III: No Benefit B-NR In patients with HCM, an invasive electrophysiological study with programmed ventricular stimulation should not be performed for risk stratification.S7.4-32,S7.4-33 III: No Benefit B-NR In patients with an identified HCM genotype in the absence of SCD risk factors, an ICD should not be implanted.S7.4-7,S7.4-34,S7.4-35 Refer to the ACCF/AHA HCM guideline for the defi- nition of HCM.S7.4-36 Recommendation-Specific Supportive Text 1. Patients with HCM have approximately a 1% risk of SCD per year.S7.4-1,S7.4-6 Selection of patients who are appropriate candidates for implanta- tion of an ICD can be a difficult clinical decision because of the individuality of each patient and family, variable definitions of risk factors and risk modifiers, sparse clinical data, the relative infre- quency of both HCM and SCD in most clinical practices, and the potential complications of liv- ing with an ICD. Table 8 lists risk factors and risk modifiers associated with SCD in patients with HCM. ICD risk stratification should be performed every 1 to 3 years in patients with HCM. There is increasing evidence supporting the association of late gadolinium enhancement on cardiac MRI with the risk of sudden death and it is included as a risk modifier.S7.4-37 S7.4-39 LV aneurysm may be Table 8.


There is increasing evidence supporting the association of late gadolinium enhancement on cardiac MRI with the risk of sudden death and it is included as a risk modifier.S7.4-37 S7.4-39 LV aneurysm may be Table 8. Major Clinical Features Associated With Increased Risk of SCD in Patients With HCM Established risk factors* Survival from a cardiac arrest due to VT or VF S7.4-1,S7.4 5,S7.4 6 Spontaneous sustained VT causing syncope or hemodynamic Family history of SCD associated with HCM S7.4 25,S7.4 26 LV wall thickness 30 mm S7.4-2,S7.4-3,S7.4 23,S7.4 24 Unexplained syncope within 6 mo S7.4 8,S7.4 26 Abnormal blood pressure response during exercise S7.4 5,S7.4 28,S7.4 29 Potential risk modifiers Delayed hyperenhancement on cardiac MRI S7.4 37 S7.4 39,S7.4 54 LVOT obstruction S7.4-2,S7.4-4 Syncope >5 y ago S7.4 8,S7.4 26 High-risk subsets LV aneurysm S7.4 40,S7.4 55,S7.4 56 *There is general agreement in the literature that these factors independently convey an increased risk for SCD in patients with HCM. Decrease in blood pressure of 20 mmHg or failure to increase systolic blood pressure >20 mmHg during exertion. There is a lack of agreement in the literature that these modifiers independently convey an increased risk of SCD in patients with HCM; however, a risk modifier when combined with a risk factor often identifies a patient with HCM at increased risk for SCD beyond the risk conveyed by the risk factor alone. A small subset of patients with an LVEF <50% (end-stage disease) or an LV aneurysm warrant consideration for ICD implantation.S7.4-52 HCM indicates hypertrophic cardiomyopathy; ICD, implantable cardioverter- defibrillator; LV, left ventricular; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; NSVT, nonsustained ventricular tachycardia; SCD, sudden cardiac death; VT, ventricular tachycardia; and VF, ventricular fibrillation.


A small subset of patients with an LVEF <50% (end-stage disease) or an LV aneurysm warrant consideration for ICD implantation.S7.4-52 HCM indicates hypertrophic cardiomyopathy; ICD, implantable cardioverter- defibrillator; LV, left ventricular; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; NSVT, nonsustained ventricular tachycardia; SCD, sudden cardiac death; VT, ventricular tachycardia; and VF, ventricular fibrillation. CLINICAL STATEMENTS AND GUIDELINES associated with a risk of sustained monomorphic Age is also an important consideration, as sudden death risk is greater in those <30 years of age, and low in patients whose initial presenta- tion is after the age of 60 years,S7.4-5,S7.4-26 2. HCM is the most common cause of SCD in individuals <40 years of age.S7.4-26 Individuals who have survived an episode of SCD, VF, or sustained VT resulting in syncope or hemodynamic compromise warrant ICD Although there are no RCTs assessing the use of the ICD in patients with HCM who have survived SCD, 1 study reported that 54% of patients with an ICD placed for secondary prevention received appro- priate ICD therapy during an average follow-up of Select patients with HCM may be candidates for implantation of the subcutaneous ; how- ever, more data on this group are needed especially given their higher risk of T wave oversensing that may increase the risk of inappropriate ICD shocks. 3. Clinical and/or genetic screening of first- and second-degree family members of patients with HCM is important to identify those with unrec- ognized disease.


Clinical and/or genetic screening of first- and second-degree family members of patients with HCM is important to identify those with unrec- ognized disease. Genetic counseling should precede genetic testing of family members to enhance their understanding of the useful- ness and cost of testing.S7.4-18,S7.4-20,S7.4-43 On the basis of family history, clinical screening, and pedigree analyses, the pattern of inheri- tance is ascertained to identify and manage relatives at risk.S7.4-13,S7.4-14,S7.4-18,S7.4-19,S7.4-43 S7.4-45 Because familial HCM is a dominant disorder, the risk that an affected patient will transmit disease to each offspring is 50%. When a pathogenic mutation is identified in an index patient, the genetic status of each family member can be readily ascertained. Relatives with overt HCM will have the same patho- genicHCMmutationastheindexpatient.Pathogenic mutations may also be identified in other relatives with unknown clinical status. These mutation- positive individuals should be evaluated by physi- cal examination, electrocardiography,S7.4-11,S7.4-17 and, if HCM is identified, these individuals should undergo risk stratification. Gene-positive subjects with- out evidence of HCM may be at risk for future development of HCM and benefit from ongoing If the proband s implicated mutation is the bona fide disease causing mutation, then mutation-negative fam- ily members and their descendants are not at an increased risk for developing HCM and do not need further evaluation. However, such muta- tion-negative family members must have an echocardiogram to ensure genotype and pheno- type concordance. 4. In a study of 1053 unrelated patients with clini- cally manifest HCM, 359 patients (34%) were genotype positive for an HCM-associated muta- tion in 1 HCM-associated genes.S7.4-22 Whether the results of genetic testing in the proband improve outcomes is uncertain, but identification Figure 7. Prevention of SCD in patients with HCM. Colors correspond to Class of Recommendation in Table 1. See Section 7.4 for discussion.


Colors correspond to Class of Recommendation in Table 1. See Section 7.4 for discussion. *ICD candidacy as determined by functional status, life expectancy, or patient preference. Risk modifiers: Age <30 y, late gadolinium enhancement on cardiac MRI, LVOT obstruction, LV aneurysm, syncope >5 y. BP indicates blood pressure; HCM, hypertrophic cardiomyopathy; Hx, history; ICD, implantable cardioverter-defibrillator; LVOT, left ventricular outflow tract; LVWT, left ventricular wall thickness; MRI, magnetic resonance imaging; NSVT, nonsustained ventricular tachycardia; SCD, sudden cardiac death; and VT, ventricular tachycardia. CLINICAL STATEMENTS AND GUIDELINES of a mutation can help inform screening of relatives. 5. Genetic counseling is important in patients with HCM, and genetic screening of relatives is also important unless there are no living first- or second-degree relatives. Most HCM is caused by an autosomal dominant mutation in genes that encode sarcomere proteins or sarcomere- associated proteins. Presence of a pathogenic sarcomere protein gene mutation in patients with HCM identifies risk of LV dysfunction and adverse outcome irrespective of the myofilament A single muta- tion in 1 of the 2 alleles (or copies) of a gene is sufficient to cause HCM; however, 5% of patients with HCM have 2 mutations in the same gene or different genes, which can be a marker for worse When genetic testing reveals a mutation in the index patient, ascertain- ment of genetic status in first- and second-degree relatives can be predictive of risk for developing Relatives with overt HCM will have the same pathogenic HCM mutation as the index patient. 6. Several studies have described an indepen- dent relationship between hypertrophy and SCD when the magnitude of hypertrophy is Risk does not abruptly increase for patients with a 30 mm wall thick- ness, but it rather increases in a linear mannerS7.4-24 and appears to carry more prognostic significance in younger patients.


Several studies have described an indepen- dent relationship between hypertrophy and SCD when the magnitude of hypertrophy is Risk does not abruptly increase for patients with a 30 mm wall thick- ness, but it rather increases in a linear mannerS7.4-24 and appears to carry more prognostic significance in younger patients. A young adult with hypertro- phy that approaches 30 mm may have similar or greater SCD risk than an older patient with maxi- mum wall thickness 30 mm.S7.4-23,S7.4-50 Patients with HCM are at an increased risk for SCD if they have a first-degree relative who expe- rienced SCD presumably caused by HCM. Family history appears to be an independent predictor of SCD although the supportive studies are small Syncope can be neu- rally mediated or medication-related as well as due to VA and requires a careful evaluation be- fore considering it a risk factor for SCD.S7.4-8,S7.4-26 In an analysis, syncope that was unexplained or thought not to be neurally mediated was associ- ated with SCD risk only when it occurred within the past 6 months but not if the most episode 7. Although sustained VT is clearly associated with SCD, the data for NSVT are less robust.


Although sustained VT is clearly associated with SCD, the data for NSVT are less robust. Most studies do not support NSVT as an inde- pendent risk factor for SCD in patients with but the risk increases if risk modifiers are present, especially in patients <30 years of age.S7.4-27 Up to one third of patients with HCM have an abnormal blood pressure response during exercise testing (defined variably as either a 20 mm Hg decrease in blood pressure or a failure to increase systolic blood pressure by at least 20 mm Hg during effort).S7.4-28,S7.4-29 This finding has been postulated to be a risk factor for SCD; how- ever, it is unclear how this relates to the increase in dynamic LV outflow tract obstruction that occurs with exertion, a hemodynamic condition that is readily modifiable with medication or mechanical procedures. The significance of an abnormal blood pressure response with exercise predicting SCD risk increases in the presence of risk modifiers (Table 8). 8. Most studies have found that NSVT alone has a low positive predictive value for SCDS7.4-2,S7.4-26, ; therefore, use of an ICD is more appropriate if risk modifiers are also present. An abnormal blood pressure response to exercise has also been associ- ated with the risk of sudden death,S7.4-5,S7.4-28,S7.4-29 but it is unclear how this relates to the increase in dynamic LV outflow tract obstruction that occurs with effort, which is often treatable. The signifi- cance of an abnormal blood pressure response with exercise for predicting SCD risk increases when risk modifiers are present (Table 8). 9.


The signifi- cance of an abnormal blood pressure response with exercise for predicting SCD risk increases when risk modifiers are present (Table 8). 9. The ICD is recommended for the prevention of SCD in patients with HCM who have survived sustained VT or VF as antiarrhythmic medications have limited effectiveness.S7.4-31 Amiodarone has been associated with improved survival in obser- vational studies and is an option for patients for whom an ICD is not feasible due to limited expec- tation for survival or patient preference.S7.4-30,S7.4-31 10. Approximately one third of consecutive patients with HCM undergoing an electrophysiologi- cal study have polymorphic VT or VF induced by programmed ventricular stimulation, but the results of programmed stimulation do not predict SCD risk. Programmed ventricular stimulation in patients with HCM has low predictive value and a nontrivial risk of complications.S7.4-32,S7.4-33,S7.4-51 Electrophysiological studies can help to clarify the diagnosis of wide complex tachycardia or guide therapy for supraventricular tachycardia or bun- dle branch reentry. 11. SCD may cluster in certain families with HCM, and the possibility that specific sarcomere muta- tions may confer SCD risk has been hypothe- sized. However, subsequent studies of selected patients with HCMS7.4-34,S7.4-35 were unable to establish a clinically useful relation between genotype and SCD risk.


However, subsequent studies of selected patients with HCMS7.4-34,S7.4-35 were unable to establish a clinically useful relation between genotype and SCD risk. In some cases, the rate of adverse events (and prevalence of associated SCD risk factors) was lower in patients with mutations initially felt to be malignant than it was in those with mutations believed to be CLINICAL STATEMENTS AND GUIDELINES Data from series of unselected consecutive outpatients suggest that most mutations are novel and limited to particular Therefore, routine mutation screening would appear to be of little prognostic value in HCM.S7.4-52 The short-term risk of sud- den death in patients who are genotype positive but have no other manifestations of the disease appears to be low.S7.4-53 Therefore, an ICD is not indicated in these individuals. Recommendations for Myocarditis References that support the recommendations are summarized in Online Data Supplement 32. 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.