National Medical Policy

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1 National Medical Policy Subject: Implantable Cardiac Event Monitors Policy Number: NMP495 Effective Date*: November 2009 Update: May 2016 ARCHIVE: NOTE: This policy has been retired. Please use DME Policy Z:\WH\Common11\ Medical Policy and Sys This National Medical Policy is subject to the terms in the IMPORTANT NOTICE at the end of this document For Medicaid Plans: Please refer to the appropriate State s Medicaid manual(s), publication(s), citation(s), and documented guidance for coverage criteria and benefit guidelines prior to applying Health Net Medical Policies The Centers for Medicare & Medicaid Services (CMS) For Medicare Advantage members please refer to the following for coverage guidelines first: Use Source Reference/Website Link X National Coverage Determination (NCD) Electrocardiographic Services (20.15): National Coverage Manual Citation Local Coverage Determination (LCD)* Article (Local)* X Other Decision Memo for Electrocardiographic Services: dver=2&ncaname=electrocardiographic+servic es&ispopup=y&bc=aaaaaaaaeaaa& CMS Manual Systems. Pub Medicare National Coverage Determinations Centers for Medicare & Medicaid Services (CMS) Transmittal 173. September 4, 2014: Implantable Cardiac Event Monitor May 16 1

2 None Guidance/Guidance/Transmittals/downloads/R17 3NCD.pdf Use Health Net Policy Instructions Medicare NCDs and National Coverage Manuals apply to ALL Medicare members in ALL regions. Medicare LCDs and Articles apply to members in specific regions. To access your specific region, select the link provided under Reference/Website and follow the search instructions. Enter the topic and your specific state to find the coverage determinations for your region. *Note: Health Net must follow local coverage determinations (LCDs) of Medicare Administration Contractors (MACs) located outside their service area when those MACs have exclusive coverage of an item or service. (CMS Manual Chapter 4 Section 90.2) If more than one source is checked, you need to access all sources as, on occasion, an LCD or article contains additional coverage information than contained in the NCD or National Coverage Manual. If there is no NCD, National Coverage Manual or region specific LCD/Article, follow the Health Net Hierarchy of Medical Resources for guidance. Current Policy Statement (Refer to Medical Policy on Mobile Outpatient Cardiac Telemetry (e.g. CardioNet for additional information) Health Net, Inc. considers the use of implantable loop recorder (ILR), cardiac event monitors (i.e., FDA approved Reveal Insertable Loop Recorders, including Reveal XT, DX, LINQ and LINQ11) medically necessary only in a limited role, in a very small subset of patients, who experience at least two episodes of recurrent, infrequent*, unexplained symptoms of pre-syncope, syncope, or tachycardia with severe symptoms of hemodynamic instability, when the following criteria are met: 1. A cardiac arrhythmia is suspected as the cause of the symptoms; and 2. A prior trial of Holter Monitor and other external ambulatory event monitors have been unsuccessful in determining a definitive diagnosis, or a diagnostic ECG. OR 3. To be used on a case by case basis only in a small subset of individuals with severely significant and suspected paroxysmal atrial fibrillation as a cause of cryptogenic stroke when other less invasive diagnostic modalities (eg, external ambulatory event monitors or Holter monitors) have been used with inconclusive results. Note*: An infrequent but recurrent symptom of pre-syncope, syncope, or tachycardia with severe symptoms of hemodynamic instability would be indicative of frequency of at least two episodes within six months. Implantable Cardiac Event Monitor May 16 2

3 Definitions ICD Implantable cardioverter defibrillator CIED Cardiac implantable electronic devices AECG Ambulatory electrocardiography ECG/EKG Electrocardiogram AHRQ Agency for Healthcare Research and Quality ACC American College of Cardiology AHA American Heart Association ILR Insertable memory loop recorder TEE Transesophageal echocardiography ESC European Society of Cardiology Committee MCOT Mobile Cardiac Outpatient Telemetry MCT Mobile cardiovascular telemetry EPS Electrophysiology studies PPM Permanent pacemakers CRT Cardiac resynchronization therapy Codes Related To This Policy NOTE: The codes listed in this policy are for reference purposes only. Listing of a code in this policy does not imply that the service described by this code is a covered or noncovered health service. Coverage is determined by the benefit documents and medical necessity criteria. This list of codes may not be all inclusive. On October 1, 2015, the ICD-9 code sets used to report medical diagnoses and inpatient procedures have been replaced by ICD-10 code sets. ICD-9 Codes Acute myocardial infarction Intermediate coronary syndrome, unstable angina Angina pectoris Other specified forms of chronic ischemic heart disease Unspecified chronic ischemic heart disease Other primary cardiomyopathies Conduction disorders Cardiac arrhythmias Syncope and collapse Dizziness and giddiness Tachycardia Palpitations ICD-10 Codes I20.0 I20.9 Angina pectoris I21.01-I21.4 ST elevation (STEMI) and non-st elevation (NSTEMI) myocardial infarction I25.5 Ischemic cardiomyopathy I25.89 Other forms of chronic ischemic heart disease I25.9 Chronic ischemic heart disease, unspecified I42.5 Other restrictive cardiomyopathy I42.8 Other cardiomyopathies I44.0-I44.7 I45.0-I45.9 I47.0-I47.9 I47.0-I47.9 Atrioventricular and left bundle-branch block Other conduction disorders Paroxysmal tachycardia Paroxysmal tachycardia Implantable Cardiac Event Monitor May 16 3

4 I48.0-I48.9 Atrial fibrillation and flutter I49.0-I49.9 Other cardiac arrhythmias R00.0 Tachycardia, unspecified R00.2 Palpitations R42 Dizziness and giddiness R55 Syncope and collapse CPT Codes Implantation of patient-activated cardiac event recorder Removal of an implantable, patient-activated cardiac event recorder External electrocardiographic recording up to 48 hours by continuous rhythm recording and storage; includes recording, scanning analysis with report, review and interpretation by a physician or other qualified health care professional External electrocardiographic recording up to 48 hours by continuous rhythm recording and storage; (includes connection, recording, and disconnection) External electrocardiographic recording up to 48 hours by continuous rhythm recording and storage; (includes scanning analysis with report) External electrocardiographic recording up to 48 hours by continuous rhythm recording and storage; review and interpretation by a physician or other qualified health care professional External mobile cardiovascular telemetry with electrocardiographic recording, concurrent computerized real time data analysis and greater than 24 hours of accessible ECG data storage (retrievable with query) with ECG triggered and patient selected events transmitted to a remote attended surveillance center for up to 30 days; review and interpretation with report interpretation by a physician or other qualified health care professional External mobile cardiovascular telemetry with electrocardiographic recording, concurrent computerized real time data analysis and greater than 24 hours of accessible ECG data storage (retrievable with query) with ECG triggered and patient selected events transmitted to a remote attended surveillance center for up to 30 days; technical support for connection and patient instructions for use, attended surveillance, analysis and transmission of daily and emergent data reports as prescribed by a physician or other qualified health care professional External patient and, when performed, auto activated electrocardiographic rhythm derived event recording with symptomrelated memory loop with remote download capability up to 30 days, 24-hour attended monitoring; includes transmission, review and interpretation by a physician or other qualified health care professional External patient and, when performed, auto activated electrocardiographic rhythm derived event recording (includes connection, recording and disconnection) External patient and, when performed, auto activated electrocardiographic rhythm derived event recording (includes transmission download and analysis) External patient and, when performed, auto activated electrocardiographic rhythm derived event recording with symptomrelated memory loop with remote download capability up to 30 days, 24-hour attended monitoring; transmission and analysis Implantable Cardiac Event Monitor May 16 4

5 93285 Programming device evaluation (in person) with iterative adjustment of the implantable device to test the function of the device and select optimal permanent programmed values with physician analysis, review and report; by a physician or other qualified health care professional; implantable loop recorder system Interrogation device evaluation (in person) with analysis review and report, includes connection, recording and disconnection per patient encounter; implantable loop recorder system, including heart rhythm derived data analysis Interrogation device evaluation(s), (remote) up to 30 days; implantable loop recorder system, including analysis of recorded heart rhythm data, analysis, review(s) and report(s)by a physician or other qualified health care professional HCPCS Codes C1764 Event recorder, cardiac (implantable) E0616 Implantable cardiac event recorder with memory, activator and programmer Scientific Rationale Update May 2016 Insertable or implantable cardiac monitors (ICMs) continuously monitor the heart rhythm and record irregularities over 3 years, enabling the diagnosis of infrequent rhythm abnormalities associated with syncope and stroke. The enhanced recognition capabilities of recent ICM models are able to accurately detect atrial fibrillation (AF) and have led to new applications of ICMs for the detection and monitoring of AF. Cryptogenic stroke describes stroke without an identifiable cause, specifically a cardioembolic source, such as a patent foramen ovale or AF. When potential cardiovascular etiologies have been ruled out during an initial workup consisting of various imaging studies and ECGs, then it's considered to be a Cryptogenic stroke. Studies on Implantable Cardiac Monitors with Suspected Atrial Fibrillation After Cryogenic Stroke Burkowitz et al. (2016) Based on a systematic literature search, two indications were identified for ICMs for which considerable evidence, including randomized studies, exists: diagnosing the underlying cardiac cause of unexplained recurrent syncope and detecting AF in patients after cryptogenic stroke (CS). Three randomized controlled trials (RCTs) were identified that compared the effectiveness of ICMs in diagnosing patients with unexplained syncope (n=556) to standard of care. A metaanalysis was conducted in order to generate an overall effect size and confidence interval of the diagnostic yield of ICMs versus conventional monitoring. In the indication CS, one RCT and five observational studies were included in order to assess the performance of ICMs in diagnosing patients with AF (n=1129). Based on these studies, there is strong evidence that ICMs provide a higher diagnostic yield for detecting arrhythmias in patients with unexplained syncope and for detection of AF in patients after CS compared to conventional monitoring. Prolonged monitoring with ICMs is an effective tool for diagnosing the underlying cardiac cause of unexplained syncope and for detecting AF in patients with CS. In all RCTs, ICMs have a superior diagnostic yield compared to conventional monitoring. Poli et al. (2015) completed a study with the goals to assess if an atrial fibrillation (AF) risk factor based pre-selection of implantable cardiac monitor (ICM) candidates would enhance the rate of AF detection and to determine AF risk factors with significant predictive value for (AF) detection. Seventy-five patients with cryptogenic IS/TIA were consecutively enrolled if at least one of the following AF risk factors was Implantable Cardiac Event Monitor May 16 5

6 present: a CHA2 DS2 -VASc score 4, atrial runs, left atrium (LA) size >45 mm, left atrial appendage (LAA) flow 0.2 m/s, or spontaneous echo contrast in the LAA. The electrocardiographic and echocardiographic criteria were chosen as they have been repeatedly reported to predict AF; the same applies for four of the six items of the CHA2 DS2 -VASc score. The study end-point was the detection of one or more episodes of AF ( 2 min). Seventy-four patients underwent implantation of an ICM; one patient had AF at the date of implantation. After 6 months, AF was detected in 21/75 patients (28%), after 12 months in 25/75 patients (33.3%). 92% of AF episodes were asymptomatic. LA size >45 mm and the presence of atrial runs were independently associated with AF detection [hazard ratio 3.6 (95% confidence interval ), P = 0.002, and 2.7 ( ), P = 0.023, respectively]. The detection rate of AF is one-third after 1 year if candidates for an ICM after cryptogenic IS/TIA are selected by AF risk factors. LA dilation and atrial runs independently predict AF. Thijs et al. (2016) assessed predictors of atrial fibrillation (AF) cryptogenic stroke (CS) or transient ischemic attack (TIA) patients who received an implantable cardiac monitor (ICM). The authors studied patients with CS/TIA who were randomized to ICM within the CRYSTAL AF study. Age, sex, race, body mass index, type and severity of index ischemic event were assessed. CHADS2 score, PR interval, and presence of diabetes, hypertension, congestive heart failure, or patent foramen ovale and premature atrial contractions predicted AF development within the initial 12 and 36 months of follow-up using Cox proportional hazards models. Among 221 patients randomized to ICM (age 61.6 ± 11.4 years, 64% male), AF episodes were detected in 29 patients within 12 months and 42 patients at 36 months. Significant univariate predictors of AF at 12 months included age (hazard ratio [HR] per decade 2.0 [95% confidence interval ], p = 0.002), CHADS2 score (HR 1.9 per one point [ ], p = 0.008), PR interval (HR 1.3 per 10 milliseconds [ ], p < ), premature atrial contractions (HR 3.9 for >123 vs 0 [ ], p = across quartiles), and diabetes (HR 2.3 [ ], p < 0.05). In multivariate analysis, age (HR per decade 1.9 [ ], p = ) and PR interval (HR 1.3 [ ], p < ) remained significant and together yielded an area under the receiver operating characteristic curve of 0.78 ( ). The same predictors were found at 36 months. Increasing age and a prolonged PR interval at enrollment were independently associated with an increased AF incidence in CS patients. However, they offered only moderate predictive ability in determining which CS patients had AF detected by the ICM. Kitsiou et al. (2016) The embolic stroke of unknown source concept was introduced as a more rigid analysis of patients with cryptogenic stroke representing a super selection of patients with cardioembolic stroke. These patients are particularly candidates for intermittent AF. As long as AF has not been documented, current concepts do not recommend oral anticoagulation. Implantable loop recorders (ILR) in patients with ESUS may detect AF and establish the indication for oral anticoagulation. The aim of this study was to prospectively assess and predict AF occurrence in patients with ILR after ESUS. In patients with ESUS (MR imaging based cardioembolic stroke, exclusion of structural cardiac stroke source by TEE, no AF detectable by 72h Stroke Unit monitoring and 24h holter ECG, exclusion of other stroke causes such as symptomatic carotid stenosis) an ILR was implanted and AF detection assessed by daily remote monitoring. The ILR was implanted on average 20 days after stroke. We analyzed the predictive value of different clinical and imaging characteristics for AF detection. By daily remote monitoring of 124 Patients over a period of 12.7±5.5 months, AF was documented and manually confirmed in 29 of 124 patients (23.4%). First AF detection occurred on average after 3.6±3.4 months of monitoring. Characteristics of patients with and without AF detection are Implantable Cardiac Event Monitor May 16 6

7 shown in the table. Patients with ESUS and asymptomatic AF detected only by longterm continuous monitoring with an ILR were on average older, had a higher CHA2DS2-VASc score and had more often microangiopathy. Other clinical parameters and features of cerebral imaging in ESUS did not increase the probability of AF detection in these preselected patients with ESUS. Importantly, ESUS selection almost doubled AF detection rate compared to recent studies such as the ILR group of the Crystal-AF trial (23.4% in 12.7±5.5 months compared to 12.4% in 12 months). Choe et al. (2015) Ischemic stroke cause remains undetermined in 30% of cases, leading to a diagnosis of cryptogenic stroke. Paroxysmal atrial fibrillation (AF) is a major cause of ischemic stroke but may go undetected with short periods of ECG monitoring. The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) demonstrated that long-term electrocardiographic monitoring with insertable cardiac monitors (ICM) is superior to conventional follow-up in detecting AF in the population with cryptogenic stroke. We evaluated the sensitivity and negative predictive value (NPV) of various external monitoring techniques within a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared to continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Shortterm monitoring included a single 24-hour, 48-hour, and 7-day Holter and 21-day and 30-day event recorders. Periodic monitoring consisted of quarterly monitoring through 24-hour, 48-hour, and 7-day Holters and monthly 24-hour Holters. For a single monitoring period, the sensitivity for AF diagnosis was lowest with a 24-hour Holter (1.3%) and highest with a 30-day event recorder (22.8%). The NPV ranged from 82.3% to 85.6% for all single external monitoring strategies. Quarterly monitoring with 24-hour Holters had a sensitivity of 3.1%, whereas quarterly 7-day monitors increased the sensitivity to 20.8%. The NPVs for repetitive periodic monitoring strategies were similar at 82.6% to 85.3%. Long-term continuous monitoring was superior in detecting AF compared to all intermittent monitoring strategies evaluated (p <0.001). Long-term continuous electrocardiographic monitoring with ICMs is significantly more effective than any of the simulated intermittent monitoring strategies for identifying AF in patients with previous cryptogenic stroke. Atrial fibrillation (AF) can be a cause of previously diagnosed cryptogenic stroke. However, AF can be paroxysmal and asymptomatic, thereby making detection with routine ECG methods difficult. Oral anticoagulation is highly effective in reducing recurrent stroke in patients with AF, but its initiation is dependent on the detection of AF. Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL AF) is the first randomized study to report the detection of AF in cryptogenic stroke patients using continuous long-term monitoring via insertable cardiac monitors (ICM). Brachman et al. (2016) completed a clinical trial with identifier of NCT Patients with prior cryptogenic stroke were randomized to control (n=220) or ICM (n=221) and followed for 36 months. Cumulative AF detection rates in the ICM arm increased progressively during this period (3.7%, 8.9%, 12.4%, and 30.0% at 1, 6, 12, and 36 months, respectively), but remained low in the control arm (3.0% at 36 months). This resulted in oral anticoagulation prescription in 94.7% of ICM patients with AF detected at 6 months, 96.6% at 12 months, and 90.5% at 36 months. Among ICM patients with AF detected, the median time to AF detection was 8.4 months, 81.0% of first AF episodes were asymptomatic, and 94.9% had at least 1 day with >6 minutes of AF. Three-year monitoring by ICM in cryptogenic stroke patients demonstrated a significantly higher AF detection rate compared with routine care. Given the frequency of asymptomatic first episodes and the long median time to detection, these findings highlight the limitations of using traditional AF detection Implantable Cardiac Event Monitor May 16 7

8 methods. The majority of patients with AF were prescribed oral anticoagulation therapy. Afzal et al. (2015) Recent studies have suggested that prolonged outpatient rhythm monitoring results in increased detection of atrial fibrillation (AF) in patients with cryptogenic stroke (CS). However, the best monitoring strategy and its clinical utility is debatable. The goal of this study was to compare the effectiveness of implantable loop recorder (ILR) versus wearable devices in identifying AF in patients with CS. Three randomized controlled trials (RCTs) and 13 observational studies were identified by database searches. Seven studies (enrolling 774 patients) employed ILR for AF detection for a median duration of 365 days (range days). Ten studies (enrolling 996 patients) employed continuous monitoring with wearable devices for a median duration of 21 days (range 4-30 days). One study performed 7 days of monitoring with wearable device followed by implantation of ILR, thus included in both groups. Pooled odds ratio (OR) of identifying AF in RCTs showed increased detection of AF with prolonged monitoring (OR 4.54, 95% confidence interval [CI] 2.92, 7.06; P < ) compared to routine outpatient follow-up. Overall detection of AF with outpatient monitoring was 17.6% (CI: ). There was significantly higher AF detection with ILR (23.3%; CI: ) compared to wearable devices (13.6%; CI: ; P < 0.05). Patients with AF were older in age compared to patients without AF. AF detection in patients with CS is improved with prolonged rhythm monitoring and is better with ILR compared to wearable devices. AF was more common in older patients. The clinical significance of these findings is unknown at this point. Ziegler et al. (2015) The characteristics of atrial fibrillation (AF) episodes in cryptogenic stroke patients have recently been explored in carefully selected patient populations. However, the incidence of AF among a large, real-world population of patients with an insertable cardiac monitor (ICM) placed for the detection of AF following a cryptogenic stroke has not been investigated. Patients in the Medtronic DiscoveryLink database who received an ICM (Reveal LINQ) for the purpose of AF detection following a cryptogenic stroke were included. AF detection rates (episodes 2 min) were quantified using Kaplan-Meier survival estimates at 1 and 6 months and compared to the CRYSTAL AF study at 6 months. The time to AF detection and maximum duration of AF episodes were also analyzed. A total of 1,247 patients (age 65.3 ± 13.0 years) were followed for 182 (IQR ) days. A total of 1,521 AF episodes were detected in 147 patients, resulting in AF detection rates of 4.6 and 12.2% at 30 and 182 days, respectively, and representing a 37% relative increase over that reported in the CRYSTAL AF trial at 6 months. The median time to AF detection was 58 (IQR ) days and the median duration of the longest detected AF episode was 3.4 (IQR ) h. The real-world incidence of AF among patients being monitored with an ICM after a cryptogenic stroke validates the findings of the CRYSTAL AF trial and suggests that continuous cardiac rhythm monitoring for periods longer than the current guideline recommendation of 30 days may be warranted in the evaluation of patients with cryptogenic stroke. The Reveal LINQ Model LNQ11 was given premarket notification by the U.S. FDA on August 5, 2015, with the 510K clearance number of K It is a small, leadless implantable device that is typically implanted under the skin, in the chest. It is an automatically-activated and patient-activated monitoring system that records subcutaneous ECG and is indicated in the following cases: Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias Implantable Cardiac Event Monitor May 16 8

9 Patients who experience transient symptoms such as dizziness, palpitation, syncope, and chest pain that may suggest a cardiac arrhythmia The device has not been tested specifically for pediatric use. Position Statements Sheldon et al. (2015) The Heart Rhythm Society (HRS), along with the American Autonomic Society (AAS), the American College of Cardiology (ACC), the American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), the European Heart Rhythm Association (EHRA), the Pediatric and Congenital Electrophysiology Society (PACES), and the Sociedad Latinoamericana de Estimulacion Cardiacay Electrofisiologia (SOLAECE) (Latin American Society of Cardiac Pacing and Electrophysiology), released a consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Implantable loop recording (ILR) is recommended for the assessment of recurrent syncope with unclear origin in older patients that are at low risk of a fatal outcome (Class IIa evidence*, level of evidence B-R). In addition, ILR monitoring is considered reasonable if an inheritable arrhythmia, cardiomyopathy, or severe bradycardia is suggested in the patient s clinical history, or if the patient is unresponsive to medical treatment. *Note: Class IIa evidence- Weight of evidence/opinion is in favor of usefulness /efficacy. Level of Evidence B - Limited evidence from single randomized trial or other nonrandomized studies. Scientific Rationale Update May 2015 Regarding implantable recorders, a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee Guideline for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death made the following recommendations regarding ambulatory electrocardiography (ECG): Implantable recorders are useful in patients with sporadic symptoms suspected to be related to arrhythmias such as syncope when a symptom-rhythm correlation cannot be established by conventional diagnostic techniques. (Level of Evidence: B) HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Patient Selection, Procedural Techniques, Patient Management and Follow-up, Definitions, Endpoints, and Research Trial Design report: Arrhythmia monitoring can be performed with the use of noncontinuous or continuous ECG monitoring tools. Choice of either method depends on individual need and consequence of arrhythmia detection. Basically, more intensive monitoring is associated with a greater likelihood of detecting both symptomatic and asymptomatic AF. They state further in the guidelines that a four-week autotrigger event monitor, mobile cardiac outpatient telemetry system, or implantable subcutaneous monitor may identify less frequent AF. Cryptogenic stroke (or stroke of undetermined origin in TOAST terminology) is defined as brain infarction that is not attributable to a source of definite cardioembolism, large artery atherosclerosis, or small artery disease despite extensive vascular, cardiac, and serologic evaluation. Cryptogenic stroke accounts for 30 to 40 percent of ischemic strokes in most modern stroke registries and databases. Per the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation:Executive Summary, Atrial fibrillation (AF) may be described by the Implantable Cardiac Event Monitor May 16 9

10 duration of the episode. Implanted loop recorders, pacemakers, and defibrillators offer the possibility of reporting frequency, rate, and duration of abnormal atrial rhythms, including atrial fibrillation (AF). Episodes often increase in frequency and duration over time. Per the American Academy of Neurology, summary of evidence-based guideline Update on prevention of stroke in nonvalvular atrial fibrillation (2014), In patients with recent cryptogenic stroke, cardiac rhythm monitoring probably detects occult nonvalvular atrial fibrillation (NVAF). Per the guideline, In patients with recent cryptogenic stroke, cardiac rhythm monitoring probably detects previously unidentified NVAF at a rate ranging from 0% to 23% (weighted average of 10.7% [95% CI 7.9% 14.3%]) (2 Class II studies, 15 Class III studies10,,24). The detection rate is probably related to the duration of monitoring. The guideline notes further, Many of the NVAF episodes that are detected are clinically asymptomatic, and thus monitoring devices with continuous recording or automatic detection algorithms, rather than patient-triggered recording, are preferred. The risk of recurrent stroke is uncertain in patients with very brief (e.g., <30 seconds) or very infrequent episodes of NVAF; however, previous studies have demonstrated that NVAF tends to occur for progressively longer periods, and the stroke risk in patients with paroxysmal NVAF is similar to that in patients with persistent NVAF. AAN Practice Recommendations include the following: Clinicians might obtain outpatient cardiac rhythm studies in patients with cryptogenic stroke without known NVAF, to identify patients with occult NVAF (Level C). Clinicians might obtain cardiac rhythm studies for prolonged periods (e.g., for 1 or more weeks) instead of shorter periods (e.g., 24 hours) in patients with cryptogenic stroke without known NVAF, to increase the yield of identification of patients with occult NVAF (Level C). Gladstone et al (2015) reported many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected AF. They sought to identify those most likely to have subclinical AF. The investigators prospectively studied patients with cryptogenic stroke or transient ischemic attack aged 55 years in sinus rhythm, without known AF, enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) trial. Participants underwent baseline 24-hour Holter ECG poststroke; if AF was not detected, they were randomly assigned to 30-day ECG monitoring with an AF autodetect external loop recorder. Multivariable logistic regression assessed the association between baseline variables (Holter-detected atrial premature beats [APBs], runs of atrial tachycardia, age, and left atrial enlargement) and subsequent AF detection. Among 237 participants, the median baseline Holter APB count/24 h was 629 (interquartile range, ) among those who subsequently had AF detected versus 45 (interquartile range, ) in those without AF (P<0.001). APB count was the only significant predictor of AF detection by 30-day ECG (P<0.0001), and at 90 days (P=0.0017) and 2 years (P=0.0027). Compared with the 16% overall 90-day AF detection rate, the probability of AF increased from <9% among patients with <100 APBs/24 h to 9% to 24% in those with 100 to 499 APBs/24 h, 25% to 37% with 500 to 999 APBs/24 h, 37% to 40% with 1000 to 1499 APBs/24 h, and 40% beyond 1500 APBs/24 h. The authors concluded among older cryptogenic stroke or transient ischemic attack patients, the number of APBs on a routine 24- hour Holter ECG was a strong dose-dependent independent predictor of prevalent subclinical AF. Those with frequent APBs have a high probability of AF and represent Implantable Cardiac Event Monitor May 16 10

11 ideal candidates for prolonged ECG monitoring for AF detection. CLINICAL TRIAL REGISTRATION: URL: Unique identifier: NCT Sanna et al (2014) states the current guidelines recommend at least 24 hours of electrocardiographic (ECG) monitoring after an ischemic stroke to rule out AF. However, the most effective duration and type of monitoring have not been established, and the cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in 20 to 40% of cases (cryptogenic stroke). Detection of AF after cryptogenic stroke has therapeutic implications. The investigators conducted a randomized, controlled study of 441 patients to assess whether long-term monitoring with an insertable cardiac monitor (ICM) is more effective than conventional followup (control) for detecting AF in patients with cryptogenic stroke. Patients 40 years of age or older with no evidence of AF during at least 24 hours of ECG monitoring underwent randomization within 90 days after the index event. The primary end point was the time to first detection of AF (lasting >30 seconds) within 6 months. Among the secondary end points was the time to first detection of AF within 12 months. Data were analyzed according to the intention-to-treat principle. By 6 months, AF had been detected in 8.9% of patients in the ICM group (19 patients) versus 1.4% of patients in the control group (3 patients) (hazard ratio, 6.4; 95% confidence interval [CI], 1.9 to 21.7; P<0.001). By 12 months, AF had been detected in 12.4% of patients in the ICM group (29 patients) versus 2.0% of patients in the control group (4 patients) (hazard ratio, 7.3; 95% CI, 2.6 to 20.8; P<0.001). The investigators concluded ECG monitoring with an ICM was superior to conventional follow-up for detecting AF after cryptogenic stroke. (Funded by Medtronic; CRYSTAL AF ClinicalTrials.gov number, NCT ). Jorfida et al (2014) reported that AF is responsible for up to one-third of ischemic strokes, and is also associated with silent cerebral infarctions and transient ischemic attacks (TIAs). The self-terminating and often asymptomatic nature of paroxysmal atrial fibrillation (PAF) may lead to its under diagnosis. A continuous and long-term heart rhythm monitoring can be useful in unmasking PAF episodes. Prevalence of asymptomatic PAF in patients suffering a cryptogenic stroke, at risk for AF but without any history of arrhythmia or palpitations, using a continuous electrocardiographic monitoring. One hundred and forty-two consecutive patients were admitted to the Stroke Unit of ' a single center between June 2010 and March 2013 and discharged with the diagnosis of ischemic cryptogenic stroke. Sixty fulfilled predefined inclusion criteria. Follow-up was carried on and completed for the 54 patients who consented to implantable loop recorder (ILR) implantation. After ILR implantation, trans-telephonic data were collected monthly. AF episodes lasting more than 5min were recorded in 25 patients (46%), median detection time was 5.4 months (range 1-18) and median duration of AF episodes was 20h (range 7min-8 days) with 19 patients (76%) remaining asymptomatic and the others experiencing weakness and dyspnoea but not palpitations. The authors concluded long-term heart rhythm monitoring is successful in unmasking silent AF in 46% of patients suffering a cryptogenic stroke with concomitant atrial fibrillation risk factors, but without history of arrhythmia or palpitations. Christensen et al (2014) reported that AF increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work-up in compliance with guidelines, up to one-third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial fibrillation (PAF) in CS remains unknown. The SURPRISE project aimed at determining this rate using long-term cardiac monitoring. Patients with CS after protocolled work-up including electrocardiography (ECG) and telemetry were included after informed consent. An implantable loop recorder (ILR) was implanted subcutaneously. PAF was defined by events of atrial arrhythmia >2 Implantable Cardiac Event Monitor May 16 11

12 min with a correlating one-lead ECG confirming the diagnosis. Eighty-five patients were monitored for a mean of 569 days (SD ±310). PAF was documented in 18 patients (20.7%) during the study period and detected by ILR in 14 patients (16.1%). In three patients PAF was detected by other methods before or after monitoring and was undiscovered due to device sensitivity in one case. The first event of PAF was documented at a mean of 109 days (SD ±48) after stroke onset. PAF was asymptomatic in all cases and occurred in episodes lasting predominantly between 1 and 4 h. Four recurrent strokes were observed, three in patients with PAF; all three patients were on oral anticoagulation (OAC). The authors concluded one in five patients with CS had PAF, which occurred at low burden and long after stroke. Future studies should determine the role of implantable cardiac monitors after stroke and determine the potential therapeutic benefit of OAC treatment of patients with PAF. Cotter et al (2013) investigated the usefulness of the ILR with improved AF detection capability (Reveal XT) and the factors associated with AF in the setting of unexplained stroke. A cohort study is reported of 51 patients in whom ILRs were implanted for the investigation of ischemic stroke for which no cause had been found (cryptogenic) following appropriate vascular and cardiac imaging and at least 24 hours of cardiac rhythm monitoring. The patients were aged from 17 to 73 (median 52) years. Of the 30 patients with a shunt investigation, 22 had a patent foramen ovale (73.3%; 95% confidence interval [CI] 56.5%-90.1%). AF was identified in 13 (25.5%; 95% CI 13.1%-37.9%) cases. AF was associated with increasing age (p = 0.018), interatrial conduction block (p = 0.02), left atrial volume (p = 0.025), and the occurrence of atrial premature contractions on preceding external monitoring (p = 0.004). The median (range) of monitoring prior to AF detection was 48 (0-154) days. The authors concluded in patients with unexplained stroke, AF was detected by ILR in 25.5%. Predictors of AF were identified, which may help to target investigations. ILRs may have a central role in the future in the investigation of patients with unexplained stroke. Rojo-Martinez et al (2013) reported that ILR s may allow detection of occult paroxysmal atrial fibrillation (PAF) in patients with cryptogenic ischemic stroke. However, optimal selection algorithm and ideal duration of monitoring remain unclear. AIM. To determine the incidence and time-profile of PAF in patients with cryptogenic ischemic stroke studied with Reveal XT ILR, who were selected based on a high suspicion of cerebral embolism. Selection criteria include the absence of stroke etiology after complete study including vascular imaging, transesophageal echocardiography and at least 24 hours of cardiac rhythm monitoring, and confirmation of acute embolic occlusion of intracranial artery by transcranial duplex or characteristics of acute ischemic lesion on neuroimaging suggesting embolic mechanism of ischemia. After implanting Reveal XT ILR, patients were trained to perform transmissions monthly or when symptoms occurred. We reviewed the information online each month and patients underwent clinical visits at 3rd and 6th month and then every six months. The authors included 101 patients with cryptogenic ischemic stroke and at least one month of follow-up after ILR implant. Mean age was 67 years, 54 women (53.5%). Mean follow-up after implantation was 281 ± 212 days. Occult PAF was detected in 34 patients (33.7%). Frequency of false positives: 22.8%. Median time from implant to arrhythmia detection was 102 days (range: days). 24 (70%) patients with PAF had several arrhythmic episodes detected with ILR. The majority of events (75%) were detected during the first six months of monitoring. The authors concluded in their patients with probably embolic cryptogenic ischemic stroke, PAF was detected by Reveal XT ILR in 33.7%. One in four events occurred after the first six months of monitoring. Implantable Cardiac Event Monitor May 16 12

13 Ziegler et al (2012) reported the detection of undiagnosed atrial tachycardia/atrial fibrillation (AT/AF) among patients with stroke risk factors could be useful for primary stroke prevention. The authors analyzed newly detected AT/AF (NDAF) using continuous monitoring in patients with stroke risk factors but without previous stroke or evidence of AT/AF. NDAF (AT/AF >5 minutes on any day) was determined in patients with implantable cardiac rhythm devices and 1 stroke risk factors (congestive heart failure, hypertension, age 75 years, or diabetes). All devices were capable of continuously monitoring the daily cumulative time in AT/AF. Of 1,368 eligible patients, NDAF was identified in 416 (30%) during a follow-up of 1.1 ± 0.7 years and was unrelated to the CHADS(2) score (congestive heart failure, hypertension [blood pressure consistently >140/90 mm Hg or hypertension treated with medication], age 75 years, diabetes mellitus, previous stroke or transient ischemic attack). The presence of AT/AF >6 hours on 1 day increased significantly with increased CHADS(2) scores and was present in 158 (54%) of 294 patients with NDAF and a CHADS(2) score of 2. NDAF was sporadic, and 78% of patients with a CHADS(2) score of 2 with NDAF experienced AT/AF on <10% of the follow-up days. The median interval to NDAF detection in these higher risk patients was 72 days (interquartile range 13 to 177). The authors concluded, continuous monitoring identified NDAF in 30% of patients with stroke risk factors. In patients with NDAF, AT/AF occurred sporadically, highlighting the difficulty in detecting paroxysmal AT/AF using traditional monitoring methods. However, AT/AF also persisted for >6 hours on 1 days in most patients with NDAF and multiple stroke risk factors. Whether patients with CHADS(2) risk factors but without a history of AF might benefit from implantable monitors for the selection and administration of anticoagulation for primary stroke prevention merits additional investigation Dion et al (2010) hypothesized that AF was involved in ischemic stroke but underdiagnosed by standard methods. They sought to determine the incidence of AF in cryptogenic ischemic stroke by using continuous monitoring of the heart rate over several months. The secondary objective was to test the value of atrial vulnerability assessment in predicting spontaneous AF. The investigators prospectively enrolled 24 patients under 75 years of age, 15 men and 9 women of mean age 49 years, who within the last 4 months had experienced cryptogenic stroke diagnosed by clinical presentation and brain imaging and presumed to be of cardioembolic mechanism. All causes of stroke were excluded by normal 12-lead ECG, 24-h Holter monitoring, echocardiography, cervical Doppler, hematological, and inflammatory tests. All patients underwent electrophysiological study. Of the patients, 37.5% had latent atrial vulnerability, and 33.3% had inducible sustained arrhythmia. Patients were secondarily implanted with an implantable loop recorder to look for spontaneous AF over a mean follow-up interval of 14.5 months. No sustained arrhythmia was found. Only one patient had non-significant episodes of AF. The authors concluded, symptomatic AF or AF with fast ventricular rate has not been demonstrated by the implantable loop recorder in patients under 75 years with unexplained cerebral ischemia. The use of this device should not be generalized in the systematic evaluation of these patients. In addition, this study attests that the assessment of atrial vulnerability is poor at predicting spontaneous arrhythmia in such patients. Schlingloff et al (2013) Recent data suggest continuous monitoring by ILR to be the criterion standard for rhythm surveillance after atrial ablation. Studies describing patient compliance and pitfalls in the perioperative period are lacking. It was the aim of this study to evaluate patient compliance and time invested by physicians for obtaining data during the follow-up period after implanting an ILR. The authors prospectively collected data of 70 consecutive patients undergoing concomitant cardiac surgery, atrial ablation, and implantation of an ILR. Patient compliance was Implantable Cardiac Event Monitor May 16 13

14 calculated as the ratio of incoming/expected data transmission. The authors documented total time spent by physicians with preoperative and postoperative supervision. Between February 2012 and February 2013, a total of 70 patients had an ILR implanted; 49 of 70 patients were eligible for evaluation of data at 3-month follow-up. The ratio of incoming/expected data transmission was 12/49 (24%). The mean ± SD time spent with ILR-related issues during hospital stay was 88 ± 19 minutes. Assessment of incoming data and information of the patient and the general practitioner took 132 ± 13 minutes per patient. Overall, a mean ± SD of 220 ± 16 minutes per patient was needed for appropriate data acquisition, from implantation to first data transmission. The authors concluded in the patients having an ILR after surgical atrial ablation, initial compliance regarding data transmission was low. A substantial time effort was necessary to obtain sufficient data on cardiac rhythm. Device-related complications were observed. Patient selection should therefore be handled with care. Beneficial therapeutic decisions can be expected only when reliable data are obtained by efficient management. Kapa et al (2013) reported arrhythmia monitoring in patients undergoing AF ablation is challenging. Transtelephonic monitors (TTMs) are cumbersome to use and provide limited temporal assessment. ILRs may overcome these limitations. The authors sought to evaluate the utility of ILRs versus conventional monitoring (CM) in patients undergoing AF ablation. Forty-four patients undergoing AF ablation received ILRs and CM (30-day TTM at discharge and months 5 and 11 postablation). Over the initial 6 months, clinical decisions were made based on CM. Subjects were then randomized for the remaining 6 months to arrhythmia assessment and management by ILR versus CM. The primary endpoint was arrhythmia recurrence. The secondary endpoint was actionable clinical events (change of antiarrhythmic drugs [AADs], anticoagulation, non-af arrhythmia events, etc.) due to either monitoring strategy. Over the study period, 6 patients withdrew. In the first 6 months, AF recurred in 18 patients (7 noted by CM, 18 by ILR; P = 0.002). Five patients in the CM (28%) and 5 in the ILR arm (25%; P = NS) had AF recurrence during the latter 6 months. AF was falsely diagnosed frequently by ILR (730 of 1,421 episodes; 51%). In more patients in the ILR compared with the CM arm, rate control agents (60% vs 39%, P = 0.02) and AADs (71% vs 44%, P = 0.04) were discontinued. The authors concluded in AF ablation patients, ILR can detect more arrhythmias than CM. However, false detection remains a challenge. With adequate oversight, ILRs may be useful in monitoring these patients after ablation. Clinical trials continue to evaluate implantable loop recorders. Numerous trials were identified on the Clinical trials.gov webpage. Scientific Rationale Update May 2014 Per the manufacturer, Medtronic, "The Reveal LINQ Insertable Cardiac Monitoring System (ICM), also known as an insertable loop recorder (ILR), is designed to help the doctor quickly diagnose and treat arrhythmias that may be related to unexplained syncope. The Reveal LINQ ICM is 1cc, the smallest heart monitor on the market; it automatically detects and records abnormal heart rhythms for up to 3 years; is safe for use in an MRI setting; is placed just under the skin of your chest in an outpatient procedure; and is not visible in most patients". Medtronic also notes that The LINQ ICM system has 20% more memory than the Reveal XT ICM, improved AF algorithms, and provides remote monitoring through the Carelink Network. This allows physicians to receive alerts about patients who are experiencing cardiac events. The Reveal LINQ includes the new MyCareLink Patient Monitor, a monitoring system using global cellular technology to transmit a patient s diagnostic data to their clinician from nearly any location in the world. Implantable Cardiac Event Monitor May 16 14

15 Medtronics has developed and manufactured various types of 'Reveal implantable cardiac monitors' including the Revel DX and XT Insertable Loop Recorders that have previously been noted within this policy statement and the scientific rationale. The Reveal LINQ insertable cardiac monitoring system (ICM) was just FDA approved with approval number K on February 14, On the FDA site it states: Summary of Substantial Equivalence: The intended use, design, materials and performance of the Reveal LINQ ICM (Model LNQI I) and Reveal Patient Assistant (Model 9538) are substantially equivalent to the following predicate devices: The Reveal XT (Model 9529) and Reveal DX (Model 9528) were initially cleared via separate 510(k) applications, reference numbers K071641, K on November 21, The Reveal XT (Model 9529) and Reveal DX (Model 9528) most recent modifications submission were cleared via K on May 4, Per the FDA site, Medtronic has demonstrated that the Reveal LINQ device described in this submission result in a substantially equivalent device because the fundamental scientific principle, operating principle, design features and intended use are unchanged from the predicate device(s). Per the FDA: The Reveal LINQ Insertable Cardiac Monitor is an implantable patientactivated and automatically-activated monitoring system that records subcutaneous ECG and is indicated in the following cases: Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias; Patients who experience transient symptoms such as dizziness, palpitation, syncope and chest pain that may suggest a cardiac arrhythmia; The Patient Assistant is intended for unsupervised patient use away from a hospital or clinic. The Patient Assistant activates the data management features in the Reveal LINQ ICM to initiate recording of cardiac event data in the implanted device memory. Scientific Rationale Update April 2014 As significant cardiac diseases increase, permanent pacemakers (PPMs), implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices are being inserted more frequently. There has also been an expansion in the indications for cardiac implantable electronic devices (i.e., CIEDs, a term which includes PPMs, ICDs, and CRT devices, as well as other devices such as implantable loop recorders and left ventricular assist devices), and device therapy has become more commonplace. The S-ICD System (Subcutaneous Implantable Cardioverter Defibrillator) received U.S. FDA approval on September 28, It is a defibrillator that is implanted subcutaneously and provides an electric shock to the heart for the treatment of ventricular tachyarrhythmias and to reduce the risks of sudden cardiac arrest (SCA) and sudden cardiac death (SCD). The S-ICD system electrode is inserted under the skin and implanted outside of the rib cage. The S-ICD System includes an implantable lead, an implantable pulse generator, a lead insertion tool, and a programming device that communicates wirelessly with the pulse generator. The pulse generator is placed in a subcutaneous pocket along the sixth rib in the left axillary area. When the device detects an arrhythmia, it confirms the finding, charges, and delivers 1 or more 80-Joule shocks to the heart. Interrogation of the Implantable Cardiac Event Monitor May 16 15