Clinical utility of implantable loop recorders.

C L I N I C A L F O C U S : C L I N I C A L P ROTO C O L S A N D C A R D I O VA S C U L A R D I S E A S E , E M E R G E N C Y S U R G E R Y, A N D E M E R G E N C Y M E D I C I N E

Clinical Utility of Implantable Loop Recorders

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DOI: 10.3810/pgm.2014.03.2738

Mahmoud Houmsse, MD 1 Abiodun Ishola, MD 2 Emile G. Daoud, MD 1 Department of Internal Medicine, Division of Cardiovascular Medicine, Ohio State University Medical Center, Columbus, OH; 2Department of Internal Medicine, Ohio State University Medical Center, Columbus, OH 1

Abstract: Implantable loop recorders provide the highest sensitivity and accuracy of diagnosing cardiac arrhythmia that results in cardiac syncope. When bradyarrhythmia or tachyarrhythmia, including atrial fibrillation, is detected, appropriate secondary prevention therapy will be implemented, which will impact the long-term clinical outcome. An implantable loop recorder enables the clinician to record for a longer period of time, which increases the likelihood of detecting cardiac arrhythmia. Currently, this technology is being evaluated to diagnose a cardiac etiology of ischemic stroke and to optimize atrial fibrillation management that will predict the success of rhythm control and prevent thromboembolic events. This article reviews implantable loop recorder technology, and discusses the current indications, the outcomes of clinical studies and ongoing current studies, and future technological improvements. Keywords: implantable loop recorder; syncope; palpitation; atrial fibrillation; cryptogenic; stroke

Introduction

Correspondence: Mahmoud Houmsse, MD, Division of Cardiovascular Medicine, The Ohio State University, Davis Heart and Lung Research Institute, 472 W 12th Avenue, Columbus, OH 43210. Tel: 614-293-4967 Fax: 614-293-5614 E-mail: [email protected]

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When evaluating patients with syncope, a major stumbling block is that the episodes are infrequent but can still be malignant, resulting in injury. Often, clinical evaluation is unrevealing and patients are then provided with an external monitor for approximately 1 month. A common result is that the patient does not have a syncopal episode during the 30 days of monitoring. To enhance diagnosing the etiology of recurrent but infrequent syncope, an implantable monitor, called an implantable loop recorder (ILR), has been developed. Because these devices are implanted subcutaneously, monitor continuously in an automatic fashion, and have a long battery life, ILRs have become an important tool for diagnosing arrhythmic etiology of recurrent syncope.1–3 In addition to being a useful diagnostic tool for syncope, multiple clinical studies are evaluating the utility of ILR for tailored therapy of atrial fibrillation (AF) rhythm or rate control strategy and anticoagulation regimens, for improving the outcomes of patients with cryptogenic stroke (CS), and for risk stratification after a myocardial infarction.4,5 This article reviews ILR technology, implantation technique and complications, clinical indications and limitations, cost and reimbursement, and future developments.

Implantable Loop Recorder Technology

The goal of ILRs is to record and store a high-quality recording of the cardiac rhythm either automatically, when the detected signal satisfies certain programmed parameters (eg, heart rate . 150 beats per minute), or via a patient-activated option when the patient is experiencing symptoms (eg, palpitations; Figure 1).6–10 Another option is that patients can use the patient activator to assess if their current rhythm satisfies

© Postgraduate Medicine, Volume 126, Issue 2, March 2014, ISSN – 0032-5481, e-ISSN – 1941-9260 ResearchSHARE®: www.research-share.com • Permissions: [email protected] • Reprints: [email protected] Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.

Clinical Utility of ILRs


Figure 1. Tracing from an ILR showing AF.

Numbers represent the length of time in milliseconds between the sensed signals that are recorded by the ILR. Abbreviation: AF, atrial fibrillation; ILR, implantable loop recorder; VS, normal ventricular conduction sensed.

certain programmed detection criteria. If so, the hand-held activator emits a color, which alerts patients to contact their physician. Each recorded event is stamped with the date and time. Because of the larger electrical amplitude, ventricular events are reliably recorded from ILRs, but the devices do not reliably record atrial events. These devices have a battery life of 2 to 3 years and store about 49 minutes of digital rhythm data.11,12 Once an event is recorded, the high-fidelity digital singlelead electrocardiogram (ECG) recording is transmitted from the device via a transmitter/modem that is provided to each patient. The patient connects the modem via a conventional land-line telephone connection, and sends the ILR information to a secure central computer system. Each device is assigned to a specific physician and only that physician’s code can access his or her patients’ ILR data via a secure Internet connection. There are currently 3 ILRs available in the United States: Reveal DX, Reveal XT, and Confirm (Figure 2). Each device can be programmed to record a rhythm automatically based primarily on heart rate criteria (eg, bradyarrhythmia of , 40 beats per minute) to detect asystole, bradycardia, and ventricular tachycardia/fibrillation.13 Reveal XT has an additional detection algorithm to enhance automatic identification of AF.14,15 Because the device does not reliably detect atrial activity, especially the low-amplitude atrial signals during AF, detection of AF is based on the expected irregular ventricular response that is characteristic of all AF episodes. Thus, rate-rhythm (R-R) variability during a 2-minute period is the primary criteria for ILRs to categorize an event as AF. If the R-R interval is regular and fixed, then atrial tachycardia or atrial flutter is detected. If the R-R interval is regular with normal heart rate modulation, then no

detection is recorded because it is considered to be a normal sinus rhythm (Figure 3).

Implantation Technique and Complications

Device implantation is rather straightforward. Just prior to device implantation, an ILR simulator can be used to map for adequate ventricular signals, or reliable signals are nearly always detected at device implantation without mapping. The device is placed in a subcutaneous pocket via a 3-cm incision in the left anterior chest of the patient, either in a parasternal location at the fourth intercostal space in a vertical Figure 2. The 2 ILR devices that are clinically available in the United States.

Abbreviation: ILR, implantable loop recorder.

© Postgraduate Medicine, Volume 126, Issue 2, March 2014, ISSN – 0032-5481, e-ISSN – 1941-9260 31 ResearchSHARE®: www.research-share.com • Permissions: [email protected] • Reprints: [email protected] Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.

Houmsee et al Figure 3. The detection algorithm utilized by ILR, based on the R-R (QRS) intervals.

Figure 4. Insertion of ILR utilizing a 3-cm incision in the anterior chest in the parasternal region.


Abbreviations: ILR, implantable loop recorder; R-R, rate-rhythm.

o rientation, or in the fifth intercostal space in a diagonal orientation. In rare situations, primarily for cosmetic concerns, the device can be placed inframammary. Implantation is performed under local anaesthesia and is completed within approximately 30 minutes (Figure 4). There are no known contraindications for the implantation of ILR; however, similar to other minor surgical procedures, other medical conditions should be considered for proper timing of device implantation. Reported patient complications include tissue rejection or reaction, skin infection, device migration, and skin erosion.16,17 The next generation of ILR technology entails a reduction of size and simplification of implantation, so that the device does not require implantation in a surgical suite but rather can be injected after local skin sterilization.

Clinical Indications and Limitations

The role of ILRs is primarily for the evaluation of patients with recurrent unexplained syncope, symptomatic arrhythmias and palpitations, or AF.

Recurrent Unexplained Syncope

Syncope is a sudden onset of temporary loss of consciousness due to hypotension that results in transient global hypoperfusion of the brain and spontaneous complete recovery.18 Syncope is the cause of 3% to 4% of emergency room visits and approximately 1% to 6% of all hospital admissions.1–3,15,19 Comprehensive history and physical examination of the patient is the cornerstone in the workup of syncope. An ECG is crucial in the evaluation of syncope. Autonomic dysfunction is the most common etiology of syncope, which includes neurally mediated syncope (vasodepressor syncope, carotid sinus hypersensitivity, and situational syncope), postural orthostatic tachycardia syndrome, and orthostatic hypotension. Arrhythmic syncope (asystole, bradyarrhythmia, and tachyarrhythmia) is the most concerning etiology of s yncope.1 This might 32


be difficult to differentiate from autonomic dysfunction.1,3 The outcome of arrhythmic syncope is worse than the other type of syncope. Patients with arrhythmic syncope have a risk of mortality . 10% within 6 months.20 Most syncopal episodes are sporadic and transient in nature, giving ECG monitoring by ILRs an advantage over brief external monitors for diagnosing the etiology of syncope. This was confirmed in the PICTURE registry study,21 which followed 570 patients with unexplained recurrent syncope. They underwent ILR implants after extensive workup, including 13 nondiagnostic tests. Syncope recurred in one third of the patients, with 78% diagnosis via ILR, which was mainly cardiac etiology. In a second study assessing the etiology of syncope among 52 patients with a bundle branch block pattern on ECG and a nondiagnostic electrophysiology study, subsequent utilization of ILR made a diagnosis of paroxysmal atrioventricular (AV) block in 42% of patients.22 An ILR is superior to conventional cardiac monitors (24-hour Holter, 30-day event, or 30-day ambulatory continuous telemetry monitors) in establishing the link between cardiac arrhythmias and syncope.1–3,19 Conventional cardiac monitors uncover the diagnosis of syncope in 20% of cases, whereas the diagnosis of the etiology could reach 88% within 5 months using ILR16 (Figure 5). Therefore, early implementation of ILR has now become an acceptable norm of practice in unexplained recurrent syncope as recommended




Figure 5. Improved diagnostic yield for patients with syncope with use of an ILR versus conventional external monitors including 24-hour Holter, 30-day event, or 30-day ambulatory continuous telemetry monitors.


in the 2009 European Society of Cardiology guidelines for the diagnosis and management of syncope.1

Symptomatic Arrhythmias and Palpitations

Implantable loop recorders have recently been approved for evaluation of symptomatic arrhythmias and p alpitations. In patients with infrequent episodes, short-term ambulatory ECG monitoring would not suffice to establish a diagnosis. Implantable loop recorders have proven to be cost-effective and highly effective in evaluation of patients with recurrent unexplained episodes of palpitations.15 A study by Giada et al15 included 50 patients with infrequent symptomatic palpitations. The patients were randomized to receive either conventional monitoring or ILR. A diagnosis was obtained in 73% of patients with ILR but in only 21% of patients with an external monitor.

Atrial Fibrillation

The ILR technology has been quite useful in the management of patients with AF who have undergone catheter ablation. Often, one of the goals of AF ablation is stopping anticoagulation. Yet, after AF ablation, patient awareness of AF episodes is reduced, and even though the patient was quite symptomatic with AF prior to ablation, after ablation the patient may have asymptomatic AF. Because this is recognized by electrophysiologists, counselling patients regarding continuation of anticoagulation presents a dilemma. Furthermore, the detection of AF by external monitors is poor. Sensitivity and negative predictive value of intermittent conventional cardiac monitoring including 24-hour Holter monitor in detecting recurrent AF after ablation of AF is lower com-

pared with ILR.23,24 Hanke et al25 confirmed this finding in a study of 45 patients who underwent surgical ablation of AF and also had implantation of an ILR. The patients then wore a 24-hour Holter monitor at 3, 6, 9, and 12 months after ablation. Sinus rhythm was noted in all 53 Holter monitors; however, ILR documented AF in 19 of these 53 readings. Therefore, a 24-hour Holter monitor failed to identify AF in 36% of patients. The ILRs (especially the Reveal XT) detect symptomatic and asymptomatic AF episodes, burden, and duration with 96.1% sensitivity and 97.4% negative predictive value.25,26 Multiple trials are evaluating the role of ILR in patients who have undergone ablation of AF to detect recurrence of AF post–catheter ablation procedures. Pokushalov et al27 evaluated the use of ILR in detecting early recurrence of AF within the first 3 months after radiofrequency ablation of AF. The follow-up was 1 year. With ILR data, 122 of 294 patients (41%) did not have AF within the first 3 months and 112 of 122 (92%) were AF free at 1 year. The reliable data from the ILR confirmed that early post–catheter ablation success translates to long-term success. Other diagnostic features that ILRs provide regarding AF episodes include a measure of AF frequency and duration (AF burden), ventricular rate during AF, and day and night heart rate to calculate daily and nightly ventricular rate burden (Figure 6).

Implantable Loop Recorder Limitations

Due to the low-amplitude signal generated by atrial activity, ILRs do not reliably record atrial events, especially if the atrial activity occurs simultaneously with ventricular events. The absence of recording atrial events makes it challenging to differentiate ventricular versus s upraventricular arrhythmias. A second limitation is under- and oversensing of electrical signals. Studies have shown that the automatic detection algorithms of ILRs are imperfect, sometimes missing ventricular tachyarrhythmias due to signal dropout, or recording muscle tremors or myopotential and classifying them as ventricular arrhythmias28 (Figure 7). Oversensing needs to be considered, especially in asymptomatic patients. Tracking the R waves using a caliper confirms the presence of regular rhythm (black dots in Figure 7) as well as the artifact signals (black arrows in Figure 7). Although ILRs are reliable, each recorded tracing must be interpreted considering the patient-specific history, rather than relying solely on the device categorization of the recorded event.


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Figure 6. An example of a summary screen provided by the ILR that notes the number of hours per day of AF, the ventricular rate in response to the atrial tachyarrhythmia, and the average ventricular rate, relative to the calendar day (on x-axis).

Abbreviations: AF, atrial fibrillation; ILR, implantable loop recorder.

Cost of External Monitors and Implantable Loop Recorders

As a device requiring surgical implantation, the initial cost of an ILR is greater than that of external monitors; however, because of the extended battery life and the need to frequently order several external monitors, the ILR is becoming

s ignificantly more cost-effective than external monitors.29,30 Examples of gross charges for external monitors and ILRs are $300 to $354 for recording, connection, disconnection, scanning, analysis, and physician interpretation of a 24-hour Holter monitor; $700 to $758 for recording, connection, disconnection, scanning, transmission download, analysis,

Figure 7. An example of an erroneous recording of what was incorrectly categorized by the ILR as rapid ventricular tachycardia.

Numbers represent the length of time in milliseconds between the sensed signals that are recorded by the ILR. Abbreviations: FD, ventricular fibrillation detected; FS, ventricular fibrillation sensed; FVT, fast ventricular tachycardia; ILR, implantable loop recorder; TS, ventricular tachycardia sensed; VS, normal ventricular conduction sensed.

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and physician interpretation of a 30-day event monitor; $900 to $1 100 for ILR surgical implantation; $700 to $800 for surgical removal of the ILR; $155 for ILR interrogation and physician interpretation.

Future Developments

With the ease of implantation and use, and the reliability of recordings, ILRs are being evaluated for utility in other clinical scenarios.


Risk Stratification Post–Myocardial Infarction

Several large clinical trials have evaluated the routine implementation of ILRs after myocardial infarction to assess risk stratification. The CARISMA (Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction) trial was an observational study that enrolled 297 patients with a left ventricular ejection fraction # 40% who received an ILR within 11 ± 5 days of an acute myocardial infarction, with a mean follow-up of 1.9 years. The study showed significant bradyarrhythmias (AV block . 8 seconds in 29 patients, sinus bradycardia in 20 patients, and sinus arrest . 5 seconds in 15 patients) and tachyarrhythmias (AF in 82 patients, nonsustained ventricular tachycardia in 38 patients, sustained ventricular tachycardia in 9 patients, and ventricular fibrillation in 8 patients) in 137 patients (46%). It is important to note that 86% of the documented arrhythmias were asymptomatic. The study also showed that development of intermittent highdegree AV block was the best predictor of mortality.4,5 The implications of the CARISMA study will be further elucidated with a subsequent study utilizing a newer ILR with enhanced atrial arrhythmia diagnostics. These studies will further demonstrate how continuous monitoring with implantable devices can improve the understanding of cardiovascular outcomes post–myocardial infarction and provide a better understanding of the efficacy of current and future therapies.4

a nticoagulation therapy is indicated and may be the proper treatment that reduces recurrences of CS. Multiple studies have utilized monitors (external and ILR) to assess for AF in patients with CS. A notable finding of these studies is that the longer the duration of cardiac monitoring, the greater the likelihood of diagnosing AF after CS. Jabaudon et al32 used a single ECG, multiple ECG recordings, a 24-hour Holter monitor, and a 7-day monitor in 149 patients who were diagnosed with CS and no history of AF. The detection of AF was highest with the 7-day monitor (16.7%) compared with 10.6% with 24-hour Holter monitor, 6.7% with multiple ECGs, and 2.7% with a single ECG. Longer duration (21 days) of external cardiac monitoring, especially with the capability of detecting asymptomatic AF, reported a higher detection rate (23%) compared with 24-hour and 7-day Holter.33 However, considering the enhanced diagnostics for AF with an ILR over external monitors for other clinical scenarios, it seems rather plausible that ILR technology will enhance the detection of AF in 28% of patients experiencing CS (Figure 8). The Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL AF) trial is exploring the utility of ILR in patients with CS to detect AF, as well as to assess the impact of anticoagulation therapy for secondary prevention of thromboembolism.34 One strategy in approaching patients with CS is to consider the CHADS2 score, which is calculated by a number of patient factors, including congestive heart failure, hypertension, age $ 75 years, diabetes mellitus, and prior episode of stroke. Studies have confirmed that the likelihood of new onset of AF is increased in patients with an elevated Figure 8. The enhanced detection of atrial fibrillation among patients with cryptogenic stroke based on the type of monitoring device and duration of monitoring.

Cryptogenic Stroke

Cryptogenic stroke (CS) is an ischemic stroke of unknown embolic source despite comprehensive evaluation. It accounts for approximately 25% to 30% of total ischemic stroke.31 The primary therapy recommended for CS is antiplatelet therapy; however, despite this therapy, the recurrence of CS is high. Considering the widespread incidence of AF and that the majority of AF episodes occur without symptoms, there is a consideration that an etiology for CS may be paroxysmal episodes of AF. If indeed AF is the mechanism, then

Abbreviations: 21-D AT EM, 21-day autotriggered event monitor; 24-H HM, 24-hour Holter monitor; 7-D EM, 7-day event monitor; ECG-1, one electrocardiogram; ECG-M, multiple electrocardiograms; ILR, implantable loop recorder.


Houmsee et al

CHADS2 score. Thus, for patients with a CS, an ILR could be considered for CHADS2 score of $ 1.35


Seizures

Implantable loop recorders should be considered in patients who have recurrent seizures despite multiple attempts at medical therapy for suppression.36 Clinical trials have shown that an estimated 20% to 30% of epileptics may be misdiagnosed, and that the etiology of the seizure is due to an arrhythmia resulting in cerebral hypoperfusion and a secondary seizure. In a study of 74 epilepsy patients who were previously diagnosed with epilepsy and who were observed with ILR, an alternative diagnosis was found in 31 patients (41.9%), including 13 of 36 (36.1%) patients taking an anticonvulsant medication, further emphasizing the importance of continuous ECG monitoring as a great diagnostic tool.36

Conclusion

Implantable loop recorders are superior to ambulatory external cardiac monitors due to their ease of implantation, ease of use by the patient, 24-hour continuous monitoring and recording of both asymptomatic and symptomatic arrhythmias based on programmed parameters or patientactivated recordings, transmission of data from home, cost-effectiveness, and prolonged battery life (3 years). The primary indication for ILR is to assist in the etiology of recurrent unexplained syncope or evaluation of symptomatic arrhythmias/palpitations. The technology of ILR is promising in other areas regarding the guidance of therapy for AF, management of patients at risk for thromboembolic events, improving outcomes of patients with CS, post–myocardial infarction risk assessment, medically refractory seizures, and unexplained falls. In general, ILRs represent a new step in medical investigation in which various types of implantable devices will improve the understanding of cardiovascular outcomes in multiple clinical settings and provide a better understanding of the efficacy of current and future therapies.

Conflict of Interest Statement

Abiodun Ishola, MD, Emile Daoud, MD, and Mahmoud Houmsse, MD, have no conflicts of interest to declare.

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