Prior Authorization Review Panel MCO Policy Submission

Transcription

1 Prior Authorization Review Panel MCO Policy Submission A separate copy of this form must accompany each policy submitted for review. Policies submitted without this form will not be considered for review. Plan: Aetna Better Health Submission Date: 07/01/2018 Policy Number: 0585 Policy Name: Cardioverter-Defibrillators Effective Date: Revision Date: 05/08/2018 Type of Submission Check all that apply: New Policy Revised Policy* Annual Review No Revisions *All revisions to the policy must be highlighted using track changes throughout the document. Please provide any clarifying information for the policy below: CPB 0585 Cardioverter-Defibrillators This CPB has been revised to include the following implantable cardioverter-defibrillator (ICD) criteria for unexplained syncope, with the presence of reproducible inducible syncopal or hypotensive VT or VF that is not associated with AMI and not due to a remediable cause, and (i) in whom antiarrhythmic medications are ineffective, not tolerated, or contraindicated, and (ii) where catheter ablation has failed or is not possible. This CPB has been revised to include the criteria for members with ischemic dilated cardiomyopathy to be at least 90 days post-revascularization (e.g., CABG, PCI with angioplasty and/or stenting) for an ICD. Name of Authorized Individual (Please type or print): Signature of Authorized Individual: Dr. Bernard Lewin, M.D.

2 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 1 of 61 ( Cardioverter-Defibrillators Number: 0585 Policy Implantable Cardioverter-Defibrillators Aetna considers Food and Drug Administrationapproved implantable cardioverter-defibrillators (thoracotomy and non-thoracotomy systems) medically necessary for any of the following groups of individuals, except where contraindicated: I. Members after one or more episodes of spontaneously occurring and inducible ventricular fibrillation (VF), or syncopal or hypotensive ventricular tachycardia (VT) that is not associated with acute myocardial infarction (AMI)]; and not due to a remediable cause (e.g., drug toxicity, electrolyte abnormalities, ischemia); or II. Members after spontaneously occurring but non-inducible documented syncopal or hypotensive VT that was not due to AMI; or Policy History Last Review 03/08/2018 Effective: 02/05/2002 Next Review: 06/13/2019 Review History Definitions Additional Information Clinical Policy Bulletin Notes

3 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 2 of 61 III. Members after VT/VF cardiac arrest that was not associated with an inducible ventricular arrhythmia, and not due to AMI; or IV. Members with structural heart disease (such as prior myocardial infarction (MI), congenital heart disease, and/or ventricular dysfunction) and spontaneous, sustained VT (greater than 30 seconds), whether hemodynamically stable or unstable; or V. Members with sustained VT (greater than 30 seconds) and normal or nearnormal ventricular function; or VI. Members after unexplained syncope, which by history and clinical circumstances was probably due to a ventricular tachyarrhythmia, with either of the following: A. the presence of reproducible inducible syncopal or hypotensive VT or VF that is not associated with AMI and not due to a remediable cause, and in whom antiarrhythmic medications are ineffective, not tolerated, or contraindicated, and where catheter ablation has failed or is not possible; CPB Cardiac Catheter Ablation see Procedures (../100_199/0165.html) ; or B. significant left ventricular (LV) dysfunction (LV ejection fraction less than 50 %), and structural heart disease such as prior myocardial infarction (MI), congenital heart disease, and/or ventricular dysfunction; or VII. Members with ischemic dilated cardiomyopathy * with any one of the following:

4 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 3 of 61 A. New York Heart Association (NYHA) Class II or III heart failure (see appendix) with a LVEF less than or equal to 35 %, who are at least 40 days post MI, and are on optimal medical therapy, defined as 3 months of maximally titrated doses as tolerated of an ACE inhibitor, beta-blocker, and diuretic, and are at least 90 days postrevascularization (e.g., CABG, PCI with angioplasty and/or stenting); or B. NYHA Class I heart failure (see appendix) with a LVEF less than or equal to 30 %, who are at least 40 days post MI, are on optimum medical therapy, and are at least 90 days post-revascularization (e.g., CABG, PCI with angioplasty and/or stenting); or C. Non-sustained VT due to prior MI, and LVEF less than or equal to 40 %, and inducible VF or sustained VT at EP study performed at least 96 hours after revascularization or MI; or VIII. Members with non-ischemic dilated cardiomyopathy, NYHA Class II or III heart failure (see appendix), and a LVEF less than or equal to 35 % who are on optimal medical therapy, defined as 3 months of maximally titrated doses as tolerated of an ACE inhibitor, beta-blocker, and diuretic; or IX. Members with familial or inherited conditions with a high-risk of life-threatening ventricular tachyarrhythmias, including: A. Long QT syndrome with either of the following: 1. Syncope and/or VT while receiving betablockers; or

5 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 4 of Asymptomatic with one or more of the following risk factors for sudden cardiac death: a. QTc greater than 500 msec, or b. LQT2 or LQT3; or c. Family history of sudden death B. Hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy (ARVC) with one or more of the following risk factors for sudden cardiac death: 1. Documented VT; or 2. Family history of sudden cardiac death in at least one first-degree relative; or 3. Left ventricular thickness of 3 cm or greater; or 4. Hypotensive response to exercise treadmill testing (ETT); or 5. At least one episode of unheralded syncope within the previous 12 months. C. Catecholaminergic polymorphic VT who have syncope and/or documented sustained VT while receiving beta-blockers. D. Brugada Syndrome who have had syncope or who have documented or inducible VT. E. LV non-compaction cardiomyopathy with either of the following: 1. Positive family history of sudden cardiac death; or

6 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 5 of Impaired left ventricular ejection fraction (less than 50 %) F. Cardiac sarcoidosis, giant cell myocarditis, or Chagas disease, regardless of LV ejection fraction G. ICD implantation may be considered in affected members with a familial cardiomyopathy associated with sudden death. * Note Ischemic cardiomyopathy is defined as left ventricular systolic dysfunction associated with marked stenosis (at least 75 % narrowing) of at least 1 of the 3 major coronary arteries, or a documented history of myocardial infarction. Aetna considers ICDs with hemodynamic (fluid status) monitoring experimental and investigational because of a lack of reliable evidence of efficacy and safety. Aetna considers the use of implantable cardioverterdefibrillators in persons with left ventricular assist devices (LVADs) experimental and investigational because the effectiveness of this approach has not been established. Notes: Aetna considerrs replacement of an implantable cardioverter defibrillator pulse generator and/or leads medically necessary when damaged, malfunctioning, when replacement is recommended according to the manufacturer's instructions in the product labeling, or due to a change in the member's medical condition.

7 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 6 of 61 Aetna considers implantable cardioverter-defibrillators experimental and investigational for other indications because its safety and effectiveness has not been established. Subcutaneous Cardioverter-Defibrillators: Aetna considers FDA-approved subcutaneous cardioverter-defibrillators medically necessary for persons who meet medical necessity criteria for an implantable cardioverter defibrillator listed above and who do not have symptomatic bradycardia, incessant ventricular tachycardia, or spontaneous, frequently recurring ventricular tachycardia that is reliably terminated with anti-tachycardia pacing or who have previous endocarditis or infection associated with conventional implantable cardioverter-defibrillators. Aetna considers subcutaneous cardioverter-defibrillators experimental and investigational for all other indications because their effectiveness and safety have not been established. Contraindications: Cardioverter-defibrillators are not considered medically necessary when other disease processes are present that clearly and severely limit the member's life expectancy. Notes: Electronic analysis of defibrillator systems is required for long-term routine follow-up care of cardioverter-defibrillators. Automatic defibrillator monitoring is considered medically necessary. Electrophysiologic assessment is a

8 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 7 of 61 more complex evaluation of cardioverterdefibrillators, and is considered medically necessary. Note: Intracardiac electrophysiological procedures performed before implantation of cardioverter-defibrillator may be done as an outpatient. See also CPB T-Wave Alternans (0579.html), CPB Biventricular Pacing (Cardiac Resynchronization Therapy)/Combination Resynchronization-Defibrillation Devices for Congestive Heart Failure and (../600_699/0610.html). Wearable Cardioverter-Defibrillators: Aetna considers wearable cardioverter-defibrillators (WCDs) (automatic external cardioverter-defibrillators that are worn under the member's clothing) medically necessary durable medical equipment (DME) only for members who meet any of the following criteria: A documented episode of VF or a sustained (lasting 30 seconds or longer) VT (these dysrhythmias may be either spontaneous or induced during an electrophysiologic (EP) study, but may not be due to a transient or reversible cause and not occur during the first 48 hours of an AMI); or A previously implanted defibrillator now requires explantation; or Member meets above-listed criteria for an ICD and is awaiting heart transplantation; or

9 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 8 of 61 Member meets above-listed criteria for an ICD and has a systemic infectious process or other temporary condition that precludes ICD implantation; or Either documented prior myocardial infarction or dilated cardiomyopathy and a measured LVEF less than or equal to 35 %; or Familial or inherited conditions with a high risk of life-threatening VT such as long QT syndrome or hypertrophic cardiomyopathy. Aetna considers WCDs experimental and investigational for use after CABG or PTCA (in persons not meeting any of the above indications) or for other indications because its safety and effectiveness has not been established. For Aetna's policy on automatic external defibrillators (AEDs) for home use, CPB Safety Items see (../600_699/0623.html). Background Cardiovascular mortality as a consequence of ventricular fibrillation (VF) or ventricular tachycardia (VT) continues to be a major health problem despite advances in the overall management of cardiovascular disease. Sudden cardiac death kills approximately 400,000 people per year. About 10 to 15 % of individuals who experience life threatening VT or VF recover, usually with an external cardiac defibrillator. These survivors have various therapeutic options such as anti-arrhythmic drugs, radiofrequency or surgical ablation of VT focus, or implantable cardioverter-defibrillators (ICDs).

10 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 9 of /13/2018 Available literature indicates ICDs are now widely used for the secondary prevention of sudden cardiac death due to VF or VT. Ventricular tachycardia or VF can be secondary to a variety of conditions: progression in underlying pathology (i.e., deterioration of left ventricular [LV] function or worsening of coronary artery disease), autonomic imbalance, electrolyte abnormalities or even pharmacological intervention. The ICD is generally accepted as treatment for patients who have experienced an episode of VF not accompanied by an acute myocardial infarction or other transient or reversible causes (e.g., drug toxicity, electrolyte abnormalities, and ischemia). Additionally, accepted guidelines prefer this treatment in patients with sustained VT causing syncope or hemodynamic compromise. As primary prevention, the literature shows the ICD is superior to conventional anti-arrhythmic drug therapy in patients who have survived a myocardial infarction and who have spontaneous, non-sustained VT, a low ejection fraction, inducible VT at electrophysiological study, and whose VT is not suppressed by procainamide. A number of well-designed studies have shown the effectiveness of the ICD in high-risk patients who have already experienced a myocardial infarction (MI). Schlapfer and colleagues (2002) compared the long-term survival rates of patients with sustained ventricular tachyarrhythmia after MI who were treated according to the results of EP study either with amiodarone or an ICD. They found that the long-term survival of patients with sustained ventricular tachyarrhythmias after MI, with depressed LV function, is significantly better with an ICD than with amiodarone therapy, even when stratified according to the results of the EP study. In a randomized controlled study (n = 1,232) to evaluate the effect of an implantable defibrillator on survival of patients with reduced LV function after MI, Moss et al (2002) concluded that in patients with a prior MI and

11 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 10 of 61 In addition, according to CMS, several additional criteria must be met. Patients must not have: New York Heart Association (NYHA) Class IV heart failure; cardiogenic shock or symptomatic hypotension while in a stable baseline rhythm; coronary artery bypass graft or percutaneous transluminal coronary angioplasty within the past 3 months; acute myocardial infarction (AMI) within the past month; clinical symptoms or findings that would make them a candidate for coronary revascularization; irreversible brain damage from prehttp://qawww.aetna.com/cpb/medical/data/500_599/0585_draft.html 06/13/2018 advanced LV dysfunction, prophylactic implantation of a defibrillator improves survival and should be considered as a recommended therapy. The Multi-center Autonomic Defibrillator Implantation Trial II (MADIT II) was stopped early because of a 30 % reduction in mortality in patients randomized to receive an ICD (Coats, 2002). The 4-year multi-center trial of 1,200 patients was terminated early after an independent board observed that the post-mi patients with impaired LV function receiving the implantable defibrillator had improved survival rates compared to those receiving conventional treatment. The Center for Medicare and Medicaid Services (CMS) determined that the evidence is adequate to conclude that an ICD is reasonable and necessary for the following: (i) patients with ischemic dilated cardiomyopathy (IDCM), documented prior MI, and a measured left ventricular ejection fraction (LVEF) of less than or equal to 35 %; (ii) patients with non-ischemic dilated cardiomyopathy (NIDCM) greater than 9 months with a measured EF less than or equal to 35 %.

12 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 11 of /13/2018 existing cerebral disease; or any disease, other than cardiac disease (e.g., cancer, uremia, liver failure) associated with a likelihood of survival less than 1 year. The Center for Medicare and Medicaid Services expanded coverage of ICDs to persons with NIDCM, based primarily on the results of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), a prospective randomized trial to determine whether amiodarone or an ICD will improve survival compared to placebo in patients with NYHA Class II and Class III heart failure and reduced LVEF less than 35 %. The study included persons with NIDCM and patients with ischemic dilated cardiomyopathy. A total of 2,521 patients were enrolled, 847 of whom were assigned to placebo plus conventional heart failure therapy, 845 to amiodarone plus conventional heart failure therapy, and 829 to single lead ICD plus conventional heart failure therapy. There was a significant reduction in all-cause mortality in the ICD group compared to the placebo group (hazard ratio compared to control = 0.77; 97.5 % confidence intervals [CI]: 0.62 to 0.96, p = 0.007). For patients with ischemic dilated cardiomyopathy, there was a reduction in mortality hazard ratio compared to control but it was not statistically significant (hazard ratio 0.79; 97.5 % CI: 0.60 to 1.04). For patients with NIDCM, there was a reduction in the mortality hazard ratio for ICD therapy compared to control but it was also not statistically significant (hazard ratio 0.73; 97.5 % CI: 0.50 to1.07). CMS noted that the absolute reduction in mortality was modest for a trial with a median follow-up of 45.5 months. Patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are characterized by progressive degeneration of the right ventricular myocardium, ventricular arrhythmias, fibrous-fatty replacement, and increased risk of sudden death.

13 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 12 of /13/2018 Mutations in 6 genes, including 4 encoding desmosomal proteins (junctional plakoglobin, desmoplakin, plakophilin 2, and desmoglein 2), have been identified in patients with ARVD/C. The potential use of genetic screening for desmoglein 2 mutations is for identifying persons at increased risk of ARVD/C who are candidates for prophylactic ICD. Currently, there are no prospective studies of the use of desmoglein 2 genetic testing for selecting ICD candidates. About one-third of individuals with ARVD/C have been reported to have mutations in the desmoglein 2 gene or other associated mutations (Franz et al, 2001), and it is unknown what proportion of asymptomatic persons who have desmoglein 2 mutations go on to develop ARVD/C. Thus, the risks and benefits of prophylactic ICD implantation in persons with mutations of this gene are unknown. Marenco et al (2001) conducted a systematic review of the literature on the use of automatic external defibrillators (AEDs). Most of the literature on AEDs discusses their use by emergency medical technician or ambulance staff. The authors summarized the literature on use of AEDs by non-medical persons in the home: Because the majority of cardiac arrests occur at home, several studies have examined the use of AEDs by family members of high-risk patients. Although these studies demonstrated the feasibility of training laypersons (e.g., family members) to use an AED, researchers had difficulty with patient recruitment and obtained disappointing results. There is mounting evidence for the efficacy of ICDs in patients at increased risk for sudden cardiac death. This has limited enthusiasm for the placement of AEDs in the home of high-risk patients and primarily limited the role of the AED in the home to high-risk patients who either refuse an ICD or have a contraindication to ICD placement. However, these studies used earlier-generation AEDs

14 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 13 of /13/2018 and, given the lower costs and ease of use of the current devices, further study with the newer technology is warranted. An assessment of AEDs for home use by the Canadian Coordinating Centre for Health Technology Assessment (CCOHTA) (Murray and Steffensen, 2005) found: No prospective studies demonstrate that the use of AEDs in the home by untrained persons improves health outcomes. Further investigation is needed to determine the benefit and harm of AEDs in the home. Because there are no prospective clinical studies demonstrating that use of AEDs by non-medical persons for home use improves health outcomes, Aetna considers wearable automatic external cardioverter defibrillators (wearable cardioverter-defibrillators or WCDs) medically necessary only on an exception basis for high-risk patients who meet the criteria for an ICD and who either refuse an ICD or have a contraindication to ICD placement. Epstein et al (2013) described usage of the WCD during mandated waiting periods following MI for patients perceived to be at high-risk for sudden cardiac arrest (SCA). These researchers evaluated characteristics of and outcomes for patients who had a WCD prescribed in the first 3 months post-mi. The WCD medical order registry was searched for patients who were coded as having had a "recent MI with ejection fraction less than or equal to 35 %" or given an International Classification of Diseases, 9th Revision 410.xx diagnostic code (acute MI), and then matched to devicerecorded data. Between September 2005 and July 2011, a total of 8,453 unique patients (age of 62.7 ± 12.7 years, 73 % male) matched study criteria. A total of 133 patients (1.6 %) received 309 appropriate shocks. Of these patients, 91 % were resuscitated from a ventricular

15 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 14 of 61 arrhythmia. For shocked patients, the LVEF was less than or equal to 30 % in 106, 30 % to 35 % in 17, greater than 36 % in 8, and not reported in 2 patients. Of the 38 % of patients not re-vascularized, 84 % had a LVEF less than or equal to 30 %; of the 62 % of patients revascularized, 77 % had a LVEF less than or equal to 30 %. The median time from the index MI to WCD therapy was 16 days. Of the treated patients, 75 % received treatment in the first month, and 96 % within the first 3 months of use. Shock success resulting in survival was 84 % in non-re-vascularized and 95 % in re-vascularized patients. The authors concluded that during the 40-day and 3-month waiting periods in patients post-mi, the WCD successfully treated SCA in 1.4 %, and the risk was highest in the first month of WCD use. The WCD may benefit individual patients selected for high risk of SCA early post-mi. The main drawback of this observational study was the lack of a control group. Additionally, quality-of-life data, cost-effectiveness and survival were not available in this study. In an accompanying editorial of the afore-mentioned study, Zei (2013) stated that A major limitation to this study is the selection bias inherent in the database used. Another important limitation of this study is the lack of data about potential arrhythmia under-detection with the WCD [T]his study still does not quite answer the elusive question of how to best risk-stratify post-mi low-ef patients in the early days after infarction. In a review on Wearable cardioverter-defibrillators, Adler et al (2013) stated that The wearable defibrillator was not subjected to such rigorous trials, and it is not clear whether this device will significantly decrease total mortality (and not merely arrhythmic death) in patients with recent MI. [W]hen the prescription of a

16 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 15 of 61 wearable defibrillator is being considered, it should be kept in mind that there are no randomized, controlled studies showing that it provides survival benefit. The first multi-center randomized controlled clinical study to examine the use of at-home AEDs found that the devices do not improve overall survival when compared to conventional resuscitation methods, such as cardiopulmonary resuscitation (CPR). Bardy et al (2008) randomly assigned 7,001 patients with previous anteriorwall MI who were not candidates for an ICD to receive 1 of 2 responses to sudden cardiac arrest occurring at home: either the control response (calling emergency medical services and performing CPR) or the use of an AED, followed by calling emergency medical services and performing CPR. The primary outcome was death from any cause. The median age of the patients was 62 years; 17 % were women. The median follow-up was 37.3 months. Overall, 450 patients died: 228 of 3,506 patients (6.5 %) in the control group and 222 of 3,495 patients (6.4 %) in the AED group (hazard ratio, 0.97; 95 % CI: 0.81 to 1.17; p = 0.77). Mortality did not differ significantly in major pre-specified subgroups. Only 160 deaths (35.6 %) were considered to be from sudden cardiac arrest from tachyarrhythmia. Of these deaths, 117 occurred at home; 58 at-home events were witnessed. Automatic external defibrillators were used in 32 patients. Of these patients, 14 received an appropriate shock, and 4 survived to hospital discharge. There were no documented inappropriate shocks. The authors concluded that for survivors of anterior-wall MI who were not candidates for ICD, access to a home AED did not significantly improve overall survival, as compared with reliance on conventional resuscitation methods. Exner (2009) stated that most sudden cardiac death (SCD) events occur in patients with less severe LV dysfunction, yet past trials and guidelines focus on those

17 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 16 of 61 with severe LV dysfunction. Given the large pool of patients with less severe LV dysfunction and a modest risk of SCD, methods to identify those who might benefit from an ICD are needed. Observational studies indicate that abnormal cardiac repolarization and impaired autonomic function, especially in combination, appear to identify patients with less severe LV dysfunction at risk of SCD. Extensive scarring also appears to identify patients at risk. Ongoing and planned studies will better define the role of using non-invasive tests to select patients for ICD therapy. The author concluded that non-invasive measures of cardiac structure, autonomic function and myocardial substrate appear to be promising in identifying patients with less severe LV dysfunction at risk of SCD. However, it is unclear if ICD therapy will improve survival in these patients. Until definitive data from prospective, randomized trials are available it is premature to recommend use of these tools to guide ICD therapy. Tsai et al (2009) noted that SCD among orthotopic heart transplant recipients is an important mechanism of death after cardiac transplantation. The role for ICDs in this population is not well-established. These researchers examined if ICDs are effective in preventing SCD in high-risk heart transplant recipients. They retrospectively analyzed the records of all orthotopic heart transplant patients who had ICD implantation between January 1995 and December 2005 at 5 heart transplant centers. A total of 36 patients were included in this study. The mean age at orthotopic heart transplant was 44 +/- 14 years, the majority being male (n = 29). The mean age at ICD implantation was 52 +/- 14 years, whereas the average time from orthotopic heart transplant to ICD implant was 8 +/- 6 years. The main indications for ICD implantation were severe allograft vasculopathy (n = 12), unexplained syncope (n = 9), history of cardiac arrest (n = 8), and severe left

18 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 17 of 61 ventricular dysfunction (n = 7). Twenty-two shocks were delivered to 10 patients (28 %), of whom 8 (80 %) received 12 appropriate shocks for either rapid VT or VF. The shocks were effective in terminating the ventricular arrhythmias in all cases. Three (8 %) patients received 10 inappropriate shocks. Underlying allograft vasculopathy was present in 100 % (8 of 8) of patients who received appropriate ICD therapy. The authors concluded that use of ICDs after heart transplantation may be appropriate in selected high-risk patients. They stated that more studies are needed to establish an appropriate prevention strategy in this population. The U.S. Food and Drug Administration (FDA) has approved the Subcutaneous Implantable Defibrillator (S-ICD) System (Cameron Health, San Clemente, CA) "to provide defibrillation therapy for the treatment of life-threatening ventricular tachyarrhythmias in patients who do not have symptomatic bradycardia, incessant ventricular~tachycardia, or spontaneous, frequently recurring ventricular tachycardia that is reliably terminated with antitachycardia pacing." The Subcutaneous Implantable Defibrillator (S-ICD) System uses a lead that is implanted just under the skin along the bottom of the rib cage and breast bone. The S-ICD System consists of: a titanium case containing a battery and electronic circuitry that provides defibrillation therapy and pacing at a rate of 50 beats per minute up to 30 seconds after a shock; a subcutaneous electrode which has a proximal and distal ring electrode on each side of a 3 inch (8 cm) defibrillation coil electrode; and accessories include an electrode insertion tool, programmer, telemetry wand, magnet, suture sleeve, torque wrench, and memory card. The FDA approval was based upon the results of a 321-patient study in which 304 patients were successfully implanted with the S-ICD System. At the time of implantation, the investigator tested the effectiveness of the device by

19 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 18 of 61 inducing heart arrhythmias. The S-ICD System was successful at converting all abnormal heart rhythms that it detected back to normal rhythms. Investigators followed these patients for six months following implantation, during which time the device detected and recorded 78 spontaneous arrhythmias in 21 patients; all arrhythmias were either successfully converted back to normal by the defibrillator or resolved on their own. The FDA noted that, because the S-ICD System memory stores data from only the 22 most recent arrhythmia episodes, there may have been other detected episodes that could not be analyzed by investigators. The FDA reviewed safety data based on the entire 321-patient study population to identify complications that can occur during and after implantation of the S-ICD System. The most common complications included inappropriate shocks, discomfort, system infection, and electrode movement, which required repositioning. The FDA reported that 8 patients died during the study; however, experts (who were not involved with the study) could not definitively attribute the deaths to the S-ICD System. Eleven patients required the removal of the device, and 18 had discomfort that was resolved without repositioning the device or surgery. At the end of six months, more than 90 percent of patients had no complications. As part of the approval, FDA is requiring the manufacturing company to conduct a postmarket study to assess the long-term safety and performance of the device and to assess differences in effectiveness across genders. The study will follow 1,616 patients for five years. There is currenty insufficient published evidence of the effectiveness and safety of this device (Bardy et al, 2010; Gold et al, 2012; Jarman et al, 2012; Kobe et al, 2012). Jarman and Todd (2013) described the early phase United Kingdom (UK) clinical experience with the S-ICD. A questionnaire was sent to all UK hospitals

20 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 19 of 61 implanting S-ICDs. Nineteen of 25 (76 %) hospitals responded with the details of 111 implanted patients (median 5/hospital [range of 1 to 18]). Mean duration of follow-up was 12.7 ± 7.1 months. Median patient age was 33 years (range of 10 to 87 years). Underlying pathology was primary electrical disease in 43 %, congenital heart disease 12 %, hypertrophic cardiomyopathy 20 %, ischemic cardiomyopathy 14 %, idiopathic dilated cardiomyopathy 5 %, and other cardiomyopathies 7 % patients. Nineteen (17 %) patients required 20 re-operations, including permanent device explantation in 10 (9 %). Twenty-four appropriate shocks were delivered in 13 (12 %) patients, including 10 for VF. One patient suffered arrhythmic death, but there were no failures to detect or terminate ventricular arrhythmias above the programmed detection rate. Fifty-one inappropriate shocks were delivered in 17 (15 %) patients; 41 (80 %) were for T-wave oversensing and 1 (2 %) for atrial flutter-wave over-sensing. The 11 patients who received inappropriate shocks due to T-wave over-sensing were significantly younger than patients who did not (24 ± 10 versus 37 ± 19 years; p = 0.02). The authors concluded that the S-ICD is an important innovation in ICD technology. However, these data indicated that adverse event rates were significant during early clinical adoption. Important lessons in patient selection, implant technique, and device programming could be learnt from this experience. In a prospective, non-randomized, multi-center trial, Weiss et al (2013) evaluated the safety and effectiveness of the S-ICD System for the treatment of life-threatening ventricular arrhythmias (VT/VF). Adult patients with a standard indication for an ICD, who neither required pacing nor had documented pace-terminable VT, were included in this study. The primary safety end-point was the 180-day S-ICD System complication-free rate

21 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 20 of 61 compared with a pre-specified performance goal of 79 %. The primary effectiveness end-point was the induced VF conversion rate compared with a pre-specified performance goal of 88 %, with success defined as 2 consecutive VF conversions of 4 attempts. Detection and conversion of spontaneous episodes were also evaluated. Device implantation was attempted in 321 of 330 enrolled patients, and 314 patients underwent successful implantation. The cohort was followed for a mean duration of 11 months. The study population was 74 % male with a mean age of 52 ± 16 years and mean LVEF of 36 ± 16 %. A previous transvenous ICD (TV- ICD) had been implanted in 13 %. Both primary endpoints were met: The 180-day system complication-free rate was 99 %, and sensitivity analysis of the acute VF conversion rate was greater than 90 % in the entire cohort. There were 38 discrete spontaneous episodes of VT/VF recorded in 21 patients (6.7 %), all of which successfully converted. Forty-one patients (13.1 %) received an inappropriate shock. The authors concluded that the findings of this study supported the safety and effectiveness of the S-ICD System for the treatment of life-threatening ventricular arrhythmias. The main drawbacks of this study were the lack of a control group and the short duration of the follow-up. In an accompanying editorial of the afore-mentioned study, Saxon noted that Over the follow-up interval reported in this study, the subcutaneous ICD terminated spontaneously occurring VT/VF in 6.5 % of the patients implanted (21 patients). There were a total of 22 episodes of spontaneously occurring monomorphic VT and 16 episodes of VF treated. First and second shock success rate was 92 % and 97 %, respectively. Two patients had multiple successful shocks for VT storm. Although these data are reassuring and comparable to TV-ICD success rates, the overall number of treated episodes is incredibly small in comparison with the data

22 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 21 of 61 on transvenous defibrillator therapies delivered outside the hospital, over the life of the device, that are available for analysis in tens of thousands of patients. Without the ability to remotely collect episodes in all subcutaneous device recipients, it is difficult to know how the learning around spontaneous VT/VF episodes and treatment will occur, other than the old-fashioned way, through case reports and post-approval registries. This is a significant limitation from a clinical learning and safety advisory perspective. Without remote monitoring capability, it will be difficult to track the occurrences of these episodes in the population of patients who receive the subcutaneous ICD. This is concerning, because the population enrolled in the subcutaneous ICD study were 10 to 20 years younger than the standard transvenous ICD recipient. The age of the subcutaneous ICD recipients indicates that they may be a more active and more prone to over-sensing owing to subcutaneous sensing challenges or T-wave double counting. Although the subcutaneous ICD is de-featured and exists only to defibrillate, it does represent a major engineering feat for an entirely subcutaneous system. Yet, the most profound technology advances in the past decades, particularly in the case of devices, allow for an enhancement of capability (and complexity) to the backend architecture and a simplification of design features and user interface. The subcutaneous ICD does not encompass these features nearly as much as the transvenous device. In the best of all possible worlds, the subcutaneous ICD will grow and evolve into a device whose design supports the growth of features and capabilities that can evolve with the patient s condition. This includes integrating wirelessly with other hardware- and software-based healthcare solutions that will enhance the device and the device recipient's overall medical condition. The enhancements will provide multiple reasons for subcutaneous ICD to exist.

23 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 22 of 61 Akerstrom et al (2013) stated that the S-ICD has recently been approved for commercial use in Europe, New Zealand and the United States. It is comprised of a pulse generator, placed subcutaneously in a left lateral position, and a parasternal subcutaneous lead-electrode with 2 sensing electrodes separated by a shocking coil. Being an entirely subcutaneous system it avoids important peri-procedural and long-term complications associated with transvenous implantable cardioverterdefibrillator (TV-ICD) systems as well as the need for fluoroscopy during implant surgery. Suitable candidates include pediatric patients with congenital heart disease that limits intra-cavitary lead placements, those with obstructed venous access, chronic indwelling catheters or high infection risk, as well as young patients with electrical heart disease (e.g., Brugada Syndrome, long QT syndrome, and hypertrophic cardiomyopathy). Nevertheless, given the absence of intra-cavitary leads, the S-ICD is unable to offer pacing (apart from shortterm post-shock pacing). It is therefore not suitable in patients with an indication for anti-bradycardia pacing or cardiac resynchronization therapy, or with a history of repetitive monomorphic VT that would benefit from anti-tachycardia pacing. Current data from initial clinical studies and post-commercialization "real-life" case series, including over 700 patients, have so far been promising and shown that the S-ICD successfully converts induced and spontaneous VT/VF episodes with associated complication and inappropriate shock rates similar to that of TV-ICDs. Furthermore, by using farfield electrograms better tachyarrhythmia discrimination when compared to TV-ICDs has been reported. The authors concluded that future results from ongoing clinical studies will determine the S-ICD system's longterm performance, and better define suitable patient profiles.

24 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 23 of 61 Pettit et al (2013) compared the performance of S-ICD and TV-ICD systems in children and teenagers. These researchers studied consecutive patients less than 20 years of age who received an ICD over a 4-year period in 2 Scottish centers. Baseline characteristics, complications, and ICD therapy were recorded. The primary outcome measure was survival. The secondary outcome measure was survival-free from inappropriate ICD therapy or system revision. A total of 9 S-ICD were implanted in 9 patients; 8 TV-ICD were implanted in 6 patients; 2 were redo procedures. Baseline characteristics were well-matched. Median duration of follow-up was lower for S-ICD (20 months) than for TV-CD (36 months, p = ). Survival was 100 % in both groups. Survival free of inappropriate therapy or system revision was 89 % for S-ICD and 25 % for TV- ICD systems (log-rank test, p = ). No S-ICD were extracted, but 3 TV- ICD were extracted due to infection (n = 1) and lead failure (n = 2). The authors concluded that in real-world use in children and teenagers, S-ICD may offer similar survival benefit to TV-CD, with a lower incidence of complications requiring reoperation. They stated that in the absence of randomized trials, S-ICD should be compared prospectively with TV-ICD in large multi-center registries with comparable periods of follow-up. Majithia et al (2014) noted that randomized clinical trials support the use of implantable defibrillators for mortality reduction in specific populations at high-risk for sudden cardiac death. Conventional transvenous defibrillator systems are limited by implantationassociated complications, infection, and lead failure, which may lead to delivery of inappropriate shocks and diminish survival. The development of a fully subcutaneous defibrillator may represent a valuable addition to therapies targeted at sudden death prevention. The PubMed database was searched to

25 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 24 of 61 identify all clinical reports of the subcutaneous defibrillator from 2000 to the present. These investigators reviewed all case series, cohort analyses, and randomized trials evaluating the safety and effectiveness of subcutaneous defibrillators. The subcutaneous defibrillator is a feasible development in sudden cardiac death therapy and may be useful particularly to extend defibrillator therapy to patients with complicated anatomy, limited vascular access, and congenital disease. The subcutaneous defibrillator should not be considered in patients with an indication for cardiac pacing or who have VT responsive to antitachycardia pacing. The authors concluded that further investigation is needed to compare long-term, head-tohead performance of subcutaneous defibrillators and conventional transvenous defibrillator systems. Furthermore, the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines on The management of STelevation myocardial infarction (O Gara et al, 2013) mentioned ICD therapy; but not subcutaneous ICD. On February 15, 2018, the Centers for Medicare & Medicaid Services (CMS) decison memo for ICDs made minimal changes to the ICD NCD to (i) require patients who have severe non-ischemic dilated cardiomyopathy but no personal history of sustained ventricular tachyarrhythmia or cardiac arrest due to ventricular fibrillation to have been on optimal medical therapy (OMT) for at least 3 months, and (ii) require a patient shared decision making (SDM) interaction prior to ICD implantation for certain patients. CMS guidelines for ICD in severe ischemic dilated cardiomyopathy include that patients must not have had a CABG, or PCI with angioplasty and/or stenting, within the past 3 months, had an MI

26 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 25 of 61 within the past 40 days, or clinical symptoms and findings that would make them a candidate for coronary revascularization. The 2017 AHA/ACC/HRS Guideline for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death includes recommendation for ICD as primary prevention of SCD in patients with ischemic heart disease with LVEF of 35% or less and who are at least 40 days post-mi, at least 90 days postrevascularization, NYHA class II or III HF despite GDMT, and meaningful survival greater than 1 year is expected. (LOE: 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 guideline-directed management and therapy (GDMT), an ICD is recommended if meaningful survival of greater than 1 year is expected. Previous Endocarditis or Device Infection as an Indication for Subcutaneous Defibrillator: De Maria et al (2014) stated the following regarding implanted and subcutaneous defibrillator: Implantable cardioverter-defibrillator: Insertion of the electrode into the central venous circulation and inside cardiac chambers can cause vascular obstruction, thrombosis, infection and cardiac perforation. Moreover, lead failure has been

27 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 26 of 61 estimated at 0.58 %/year and up to 20 % at 10 years; failures may require the leads to be extracted, however this is a highly challenging procedure: major complications rates are about 1 % and mortality is at 0.3 %, even in experienced centers. Subcutaneous defibrillator: The risk of systemic infections appears to be very low, best in high-risk cases of previous device infection, hemodialysis, chronic immunosuppression therapy immunodeficiencies, or artificial heart valves. Subcutaneous defibrillator as first choice -- Previous endocarditis or device infection Also, an UpToDate review on Subcutaneous implantable cardioverter defibrillators (Weinstock et al, 2015) states that ICD systems consist of a pulse generator, typically placed in the pectoral region, and one or more leads which attach the pulse generator to the heart, most commonly to the endocardium via transvenous insertion. However, conventional transvenous ICD (TV-ICD) systems come with the inherent drawbacks of transvenous leads, including: Risks at the time of insertion -- Cardiac perforation, pericardial effusion, cardiac tamponade, hemothorax, pneumothorax Delayed risks over the lifetime of the device -- Intravascular lead infection, lead failure Reports of complications at the time of TV-ICD range from 3 to 6 % of implants. In addition, the delayed risks of transvenous leads include a risk of infection (incidence of 9 per 1,000 device-years) and lead failure (ranging from 5 to 40 %of leads at 5 years depending on the type of lead), both of which lead to repeat procedures

28 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 27 of 61 and increased morbidity for patients. The subcutaneous implantable cardioverter defibrillator (S-ICD) system obviates some of the mechanical complications associated with transvenous lead implantation (e.g., cardiac perforation leading to pericardial effusion and cardiac tamponade, hemothorax, pneumothorax, endovascular lead infection). Defibrillation Threshold (DFT) Testing During Implantable Cardioverter-Defibrillator Implantation: Gula et al (2008) noted that defibrillation threshold (DFT) testing is generally performed during implantation of ICDs to assess sensing and termination of VF. It is common clinical practice to defibrillate VF twice at an output at least 10 J below the maximum output of the device, providing a 10 J safety margin. However, there are few data regarding impact of DFT testing on outcomes. These investigators evaluated the impact of DFT testing of implanted ICDs on survival. Decision analysis and Monte Carlo simulation were used to assess expected outcomes of DFT testing. Survival of a hypothetical cohort of patients was assessed according to 2 strategies-routine DFT testing at time of ICD implant versus no DFT testing. Assumptions in the model were varied over a range of reasonable values to assess outcomes under a variety of scenarios. Five-year survival rates with DFT and no-dft strategies were similar at % and %, respectively. The results were not sensitive to changing risk estimates for arrhythmia incidence and safety margin. Results of the Monte Carlo simulation were qualitatively similar to the base case scenario and consistent with a small and nonsignificant survival advantage with routine DFT testing. The authors concluded that the impact of DFT testing on 5-year survival in ICD patients, if it exists, is small. Survival appears higher with DFT testing as long as

29 Cardioverter-Defibrillators - Medical Clinical Policy Bulletins Aetna Page 28 of 61 annual risk of lethal arrhythmia or the risk of a narrow safety margin is at least 5 %, although the incremental benefit is marginal and 95 % CIs cross zero. They stated that a prospective randomized study of DFT testing in modern devices is warranted. Bianchi et al (2009) compared the outcome of ICD recipients who underwent DFT testing with that of patients in whom no testing was performed. A total of 291 subjects with ischemic dilated cardiomyopathy received transvenous ICDs between January 2000 and December 2004 in 5 Italian cardiology centers were included in this study. In 2 centers, DFT testing was routinely performed in 137 patients (81 % men; mean age of 69 +/- 9 years; mean ejection fraction of 26 +/- 4 %) (DFT group), while 3 centers never performed DFT testing in 154 patients (90 % men; mean age of 69 +/- 9 years; mean ejection fraction of 27 +/- 5 %) (no-dft group). These researchers compared total mortality, total cardiovascular mortality, SCD, and spontaneous episodes of ventricular arrhythmia (sustained ventricular tachycardia, VT, and ventricular fibrillation, VF) between these groups 2 years after implantation (median of 23 months; 25 th to 75th percentile; 12 to 44 months). On comparing the DFT and no-dft groups, these investigators found an overall mortality rate of 20 % versus 16 %, cardiovascular mortality of 13 % versus 10 %, SCD of 3 % versus 0.6 %, VT incidence of 8 % versus 10 %, and VF incidence of 6 % versus 4 % (no significant difference in any comparison). The authors concluded that no significant differences in the incidence of clinical outcomes