Advertisement

2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry

      Abstract

      Ambulatory ECG (AECG) is very commonly employed in a variety of clinical contexts to detect cardiac arrhythmias and/or arrhythmia patterns which are not readily obtained from the standard ECG. Accurate and timely characterization of arrhythmias is crucial to direct therapies that can have an important impact on diagnosis, prognosis or patient symptom status. The rhythm information derived from the large variety of AECG recording systems can often lead to appropriate and patient-specific medical and interventional management. The details in this document provide background and framework from which to apply AECG techniques in clinical practice, as well as clinical research.

      Keywords

      1. Introduction

      Ambulatory ECG (AECG)
      Synonymously termed Holter and continuous ECG monitoring. We have elected to consistently use “AECG” for this document.
      telemetry is typically used to evaluate symptoms such as syncope, dizziness, chest pain, palpitations, or shortness of breath, which may correlate with intermittent cardiac arrhythmias. Additionally, AECG is used to evaluate patient response to initiation, revision, or discontinuation of arrhythmic drug therapy and to assess prognosis in specific clinical contexts. The purposes of this statement were (1) to review how contemporary AECG devices acquire and process ECG signals and how they should be interpreted; (2) to review appropriate utilization of these devices in the management of cardiovascular disease; and (3) to promote standards that will improve the accuracy and appropriate use of the AECG in clinical practice.
      The writing group recognizes that technical details of the processing and recording of AECGs may be unfamiliar to some clinicians. Accordingly, a major purpose of this document was to provide clinicians with insight concerning current technology and its implications for clinical interpretation. Moreover, evolving technologies permit integration of cardiac data with other monitored variables, extending traditional applications.
      This document builds upon previous published professional society guidelines from 1999 to 2009 (
      • Brignole M.
      • Vardas P.
      • Hoffman E.
      • Huikuri H.
      • Moya A.
      • Ricci R.
      • Wieling O.
      Indications for the use of diagnostic implantable and external ECG loop recorders.
      ,
      • Crawford M.H.
      • Bernstein S.J.
      • Deedwania P.C.
      • DiMarco J.P.
      • Ferrick K.J.
      • Garson Jr., A.
      • Smith Jr., S.C.
      ACC/AHA guidelines for ambulatory electrocardiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography). Developed in collaboration with the North American Society for Pacing and Electrophysiology.
      ,
      • Drew B.J.
      • Califf R.M.
      • Funk M.
      • Kaufman E.S.
      • Krucoff M.W.
      • Laks M.M.
      • Van Hare G.F.
      American Heart Association; Councils on Cardiovascular NursingClinical Cardiologyand Cardiovascular Disease in the Young
      AHA Scientific Statement: Practice standards for electrocardiographic monitoring in hospital settings.
      ,
      • Kadish A.H.
      • Buxton A.E.
      • Kennedy H.L.
      • Knight B.P.
      • Mason J.W.
      • Schuger C.D.
      • Weitz H.H.
      ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography. A report of the ACC/AHA/ACP-ASIM Task Force on Clinical Competence (ACC/AHA Committee to Develop a Clinical Competence Statement on Electrocardiography and Ambulatory Electrocardiography).
      ), and focuses most intently on the evolution and advancement of AECG technology and its impact on clinical decision making and practice.

      2. Methodology of Document Preparation

      The writing committee consisted of experts in the field representing the International Society for Holter and Noninvasive Electrocardiology (ISHNE) and Heart Rhythm Society (HRS). The authors performed exhaustive literature searches to develop and ultimately provide recommendations regarding appropriate technology for AECG monitoring and its clinical applications. The final recommendations were reviewed by all writing committee members, and each member voted for inclusion with the vote threshold set at 80%. Recommendation classes and level of evidence presented in this document follow 2014 ACC/AHA standards (
      • Jacobs A.K.
      • Anderson J.L.
      • Halperin J.L.
      The evolution and future of ACC/AHA clinical practice guidelines: A 30-year journey: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
      ) with recent modifications.

      3. Section 1: Modalities, Technology, and Equipment

       3.1. Ambulatory ECG monitoring techniques and systems

      External AECG serves to detect, document, and characterize abnormal cardiac activity during ordinary daily activities, extending the role of ECG recording beyond the bedside 10-s standard 12-lead resting ECG (
      • Crawford M.H.
      • Bernstein S.J.
      • Deedwania P.C.
      • DiMarco J.P.
      • Ferrick K.J.
      • Garson Jr., A.
      • Smith Jr., S.C.
      ACC/AHA guidelines for ambulatory electrocardiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography). Developed in collaboration with the North American Society for Pacing and Electrophysiology.
      ,
      • Kadish A.H.
      • Buxton A.E.
      • Kennedy H.L.
      • Knight B.P.
      • Mason J.W.
      • Schuger C.D.
      • Weitz H.H.
      ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography. A report of the ACC/AHA/ACP-ASIM Task Force on Clinical Competence (ACC/AHA Committee to Develop a Clinical Competence Statement on Electrocardiography and Ambulatory Electrocardiography).
      ). AECG technology is noninvasive, easy to use, relatively inexpensive, and readily available.
      Pioneering work by Norman “Jeff” Holter led to the first prototype of “mobile” cardiac telemetry device, requiring 85 pounds of equipment, worn on his back while riding a stationary bicycle and used a radio-ECG (circa 1947) (
      • Del Mar B.
      The history of clinical Holter monitoring.
      ,
      • Kennedy H.L.
      The history, science and innovation of Holter technology.
      ). Modern AECG devices are light and inconspicuous, and through continuous beat-to-beat ECG monitoring, automatic arrhythmia detection and wireless transmission of data in near real time improve diagnostic yield and provide enormous improvements in efficiency and ease of use (
      • Charitos E.I.
      • Stierle U.
      • Ziegler P.
      • Baldewig M.
      • Robinson D.
      • Sievers H.
      • Hanke T.
      A comprehensive evaluation of rhythm monitoring strategies for the detection of atrial fibrillation recurrence: Insights from 647 continuously monitored patients and implications for monitoring after therapeutic interventions.
      ,
      • Hanke T.
      • Charitos E.I.
      • Stierle U.
      • Karluss A.
      • Kraatz E.
      • Graf B.
      • Sievers H.H.
      Twenty-four-hour Holter monitor follow-up does not provide accurate heart rhythm status after surgical atrial fibrillation ablation therapy: Up to 12 months experience with a novel permanently implantable heart rhythm monitor device.
      ,
      • Locati E.T.
      • Moya A.
      • Oliveira M.
      • Tanner H.
      • Willems R.
      • Lunati M.
      • Brignole M.
      External prolonged electrocardiogram monitoring in unexplained syncope and palpitations: Results of the SYNARR-Flash study.
      ,
      • Mittal S.
      • Movsowitz C.
      • Steinberg J.S.
      Ambulatory external electrocardiographic monitoring: Focus on atrial fibrillation.
      ,
      • Reiffel J.
      • Schwarzberg R.
      • Murry M.
      Comparison of autotriggered memory loop recorders versus standard loop recorders versus 24-hour Holter monitors for arrhythmia detection.
      ,
      • Rosenberg M.A.
      • Samuel M.
      • Thosani A.
      • Zimetbaum P.J.
      Use of a noninvasive continuous monitoring device in the management of atrial fibrillation: A pilot study.
      ,
      • Rothman S.
      • Laughlin J.
      • Seltzer J.
      • Walia J.
      • Baman R.
      • Siouffi S.
      • Kowey P.
      The diagnosis of cardiac arrhythmias: A prospective multicenter randomized study comparing mobile cardiac outpatient telemetry versus standard loop event monitoring.
      ,
      • Vasamreddy C.R.
      • Dalal D.
      • Dong J.
      • Cheng A.
      • Spragg D.
      • Lamiy S.Z.
      • Calkins H.
      Symptomatic and asymptomatic atrial fibrillation in patients undergoing radiofrequency catheter ablation.
      ).
      Miniaturization of instrumentation is progressing rapidly in concert with evolution of microelectronic circuits (
      • Soundarapandian K.
      • Berarducci M.
      Analog front-end design for ECG systems using delta-sigma ADCs.
      ) accompanied by evolution of wireless networking technologies and in particular the emergence of secure Smart Bluetooth (ver. 4.2) optimized for medical applications. Some AECG devices also feature multiple biological signal sensors that allow for simultaneous recording of multilead ECGs along with respiratory rate, peripheral oxygen saturation, physical activity, skin temperature, arterial pulse pressure, and other parameters, to provide the comprehensive evaluation of patients with complex disorders, such as heart failure or sleep apnea syndromes (
      • Locati E.T.
      Advances in modern electrocardiographic equipment for long-term ambulatory monitoring.
      ). These sensors extend AECG functions from simply ECG to include ambulatory vital signal monitoring.
      Challenges persist for both manufacturers and clinicians to provide reliability and functionality, yet handle transmissions and analyze and store large amounts of data securely. In asymptomatic patients and situations when abnormalities occur infrequently, AECG devices capable of very long recording periods of up to several weeks and even months can be used. Poor tolerability of wire-electrode systems (especially when recording is prolonged) and adverse skin reactions challenge patient compliance. Table 1 and Figure 1 summarize some characteristics of modern AECG monitoring devices.
      Table 1Characteristics of ambulatory cardiac monitoring devices
      Duration of recording<1 min24–48 hr3–7 days1–4 weeks≤36 months
      Types of recorderExternal event recorderStandard Holter recorderImplantable loop recorder
      Smartphone-based recorderMobile cardiac telemetryPatch/Vest/Belt recorderPatch/Vest/Belt recorder
      Mobile cardiac telemetryExternal loop recorder
      Event loop recorderMobile cardiac telemetry
      Modality of recording
       Event recording
       Continuous recording
       Autotrigger recording
      Number of recording leads
       1 lead (2 electrodes)
       2 leads (3 electrodes)
       3 leads (5–7 electrodes)
       12 leads (10 electrodes)
      Type of recording system
       Adhesive wired electrodes
       Patch/Vest/Belt wireless system
       Built-in electrodes
      Available analyses
       Arrhythmia analysis
       ST analysis
       HRV—Heart rate variability
       QT dynamicity
       HRT—Heart rate turbulence
       HDR—Holter-derived respiration
       QRS late potentials
       P-wave averaging
       T-wave variability
       Activity level
      Frequency of symptoms should dictate the type of recording: longer term ECG monitoring is required for more infrequent events. Correlation (or lack of) of symptoms and arrhythmias is key. The most appropriate clinical workflow may include a continuous (short-term 24 hr and up to 7 days) AECG monitoring, which if unsuccessful, is followed by intermittent external loop recording (long-term from weeks to months). For those patients remaining undiagnosed after prolonged noninvasive monitoring, implantable loop recorders (ILR) may be necessary.
      Figure thumbnail gr1
      Figure 1Types of AECG monitors currently available in clinical practice. (A) Holter, event, and loop monitoring; (B) patch-type extended Holter and ambulatory telemetry monitoring AECG, ambulatory external electrocardiographic; ECG, electrocardiographic. Figure illustration by Craig Skaggs.
      Reproduced with permission from
      • Mittal S.
      • Movsowitz C.
      • Steinberg J.S.
      Ambulatory external electrocardiographic monitoring: Focus on atrial fibrillation.
      .

       3.1.1. Continuous single and multilead external recorders wire-lead transmission (Holter monitors)

      Ambulatory ECG recorders are typically small, lightweight devices (200–300 gm) that use soft wire patient cables and standard wet gel electrodes worn continuously to record ECG data. Recordings may be in 2-channel (two independent bipolar leads), 3-channel, 12-channel, or EASI lead formats. Although traditionally used for 24–48 hr, some newer generation devices permit recording periods up to 30 consecutive days.
      Traditional AECG recorders require active patient participation. Patients may manually record in a diary or mark the occurrence of symptoms by pressing a built-in switch on the recorder. AECG data are analyzed postrecording on a dedicated workstation.

       3.1.2. Continuous single- or two-lead external recorders with wireless transmission (patch ECG monitors)

      Wearable adhesive “patch ECG monitors” constructed with embedded electrodes, with wireless data transmission, are a new class of AECG recording devices (
      • Lobodzinski S.S.
      ECG patch monitors for assessment of cardiac rhythm abnormalities.
      ,
      • Lobodzinski S.S.
      • Laks M.M.
      New devices for very long-term ECG monitoring.
      ). These on-skin wearable devices, which remove the need for patient cable wires and discrete electrodes, can record 1- or 2-lead electrogram from two closely spaced electrodes worn continuously for up to 14 days. A compact, lightweight patch affixed over the patient's left pectoral region is comfortable to wear and does not interfere with patients' daily routines as it is water resistant and can remain on the patient during showering and exercise. Patients can press a button to mark symptomatic episodes. Proprietary algorithms diagnose cardiac rhythms based on beat-by-beat QRS detection. Up to 7–14 days of ambulatory monitoring yields a high rate of arrhythmia identification (
      • Rosenberg M.A.
      • Samuel M.
      • Thosani A.
      • Zimetbaum P.J.
      Use of a noninvasive continuous monitoring device in the management of atrial fibrillation: A pilot study.
      ,
      • Turakhia M.P.
      • Hoang D.D.
      • Zimetbaum P.
      • Miller J.D.
      • Froelicher V.F.
      • Kumar U.N.
      • Heidenreich P.A.
      Diagnostic utility of a novel leadless arrhythmia monitoring device.
      ). Newer patch ECG monitors are also capable of recording body temperature, patient activity, respiration, and galvanic skin reflex (
      • Ajami S.
      • Teimouri F.
      Features and application of wearable biosensors in medical care.
      ). Adhesive ECG patch devices with embedded electrodes and sensor shirts featuring textile electrodes (sometimes called “textrodes”) are better accepted by the patients and improve compliance with extended monitoring (
      • Lobodzinski S.S.
      ECG patch monitors for assessment of cardiac rhythm abnormalities.
      ,
      • Lobodzinski S.S.
      • Laks M.M.
      Comfortable textile-based electrocardiogram systems for very long-term monitoring.
      ,
      • Lobodzinski S.S.
      • Laks M.M.
      New devices for very long-term ECG monitoring.
      ,
      • Perez de Isla L.
      • Lennie V.
      • Quezada M.
      • Guinea J.
      • Arce C.
      • Abad P.
      • Zamorano J.
      New generation dynamic, wireless and remote cardiac monitorization platform: A feasibility study.
      ).

       3.1.3. Intermittent external patient- or event-activated recorders (external loop recorders)

      Intermittent autotriggered loop recorders are typically single bipolar lead devices. Loop recording is generally performed over longer periods, ranging from weeks to months. Continuous memory-loop recorders are often equipped with an autotrigger function that captures the “prior-to-event to postevent” portion of the ECG signal into the device memory. Intermittent loop recorders can be either external devices (“external loop recorder” or ELR) or implantable devices (“implantable loop recorder” or ILR) (
      • Brignole M.
      • Vardas P.
      • Hoffman E.
      • Huikuri H.
      • Moya A.
      • Ricci R.
      • Wieling O.
      Indications for the use of diagnostic implantable and external ECG loop recorders.
      ). Both ELR and ILR record ECG tracings lasting from few seconds to several minutes (in some cases up to 1 hr, to include the onset and offset of arrhythmias) and can detect both symptomatic and asymptomatic arrhythmias (by means of autotrigger functions). ELR and ILR detect, record, and store the occurrence of infrequent specific rhythm disorders (such as pauses, bradycardia, supraventricular, and ventricular arrhythmias). ELRs need to be worn continuously by the patient and are attached to the chest by a variety of carrier systems that include wire electrodes. Upon event detection, ECG data are stored for a predefined amount of time prior to the event (looping memory) and a period of time after the activation. As documented by SYNARR-Flash study, prolonged 4-week ELR monitoring has a high yield for evaluation of syncope and palpitations (
      • Locati E.T.
      • Moya A.
      • Oliveira M.
      • Tanner H.
      • Willems R.
      • Lunati M.
      • Brignole M.
      External prolonged electrocardiogram monitoring in unexplained syncope and palpitations: Results of the SYNARR-Flash study.
      ).

       3.1.4. Intermittent external patient- or automatically activated postevent recorders (external event recorders)

      Simpler nonlooping postevent recorders are not worn continuously. Rather, these portable devices with built-in electrodes are applied directly on the chest (or held by both hands) to record a very brief duration single-lead ECG signal during symptoms. Recently, new smartphone-based ECG recording systems have been developed (
      • Haberman Z.C.
      • Jahn R.T.
      • Bose R.
      • Tun H.
      • Shinbane J.S.
      • Doshi R.N.
      • Saxon L.A.
      Wireless smartphone ECG enables large-scale screening in diverse populations.
      ). These record a single-lead electrogram from closely spaced stainless steel electrodes embedded into the smartphone-holding case (also see Section 9). Patient-activated postevent recorders have the potential to transmit the “near-real-time” event ECG data, provided patients recognize symptoms and activate the recording in a timely fashion. The event data are transmitted usually via digital cell phone networks directly to the data monitoring center for immediate analysis. Notification alarms are also generated and sent directly to the caregivers.

       3.1.5. External real-time cardiac telemonitoring systems—mobile cardiac telemetry

      Mobile cardiac telemetry (MCT) devices combine the benefits of AECG recorders, ELRs, and nonlooping event recorders. Often, these are single-lead electrogram recording devices embedded either in a patch, necklace pendant, or a chest belt carrier, as well as conventional ECG electrodes. Worn continuously, these devices are capable of real-time streaming, transmitting a loop, or a single-event electrogram directly to the reading center via a wireless link. Newest iterations can connect to any WiFi access point to transfer data.
      The MCT data are processed in a reading center on the back end of the monitoring system. The arrhythmic events are analyzed by trained technicians, and alarms are distributed to the caregivers. MCT devices are also equipped with real-time signal processing algorithms providing detection of cardiac arrhythmias. Some MCTs use a multilead standard 3-channel Holter-like recording wire-electrode systems (
      • Rothman S.
      • Laughlin J.
      • Seltzer J.
      • Walia J.
      • Baman R.
      • Siouffi S.
      • Kowey P.
      The diagnosis of cardiac arrhythmias: A prospective multicenter randomized study comparing mobile cardiac outpatient telemetry versus standard loop event monitoring.
      ,
      • Tsang J.P.
      • Mohan S.
      Benefits of monitoring patients with mobile cardiac telemetry (MCT) compared with the Event or Holter monitors.
      ).

       3.1.6. Selection of appropriate technologies

      The selection of appropriate technology has to take into account diagnostic power, monitoring, and risk stratification accuracy with consideration about cost-effectiveness, patient acceptance, degree of automaticity, and local availability and experience, as well as, symptom frequency, the overall patient clinical condition, and the probability of life-threatening arrhythmia (Tables 1 and 2). MCT provides the benefit of real-time, comprehensive data without requiring the patient to participate in the process of data transmission. Unlike AECG recorders, these devices allow immediate transmission of information; compared with looping event recorders, they gather more information and allow remote data transfer while overcoming the technical challenges of data transmission. This large amount of real-time data affords a higher diagnostic yield than standard devices but places a potential burden on the clinician who must be available to review large amounts of information (e.g., daily) at any time of the day or night. Conversely, standard AECG monitoring devices and loop recorders are inexpensive and readily available. The need for ECG resolution may direct choice of Holter versus patch electrodes. Major advantages and limitations of AECG techniques are summarized in Table 3.
      Table 2Estimated diagnostic yield of different AECG recording modalities
      Duration of recordingType of recorderPalpitations (%)Syncope (%)Cryptogenic stroke (%) (Silent AF)
      <60 sEvent recorder50–60Not applicableNot applicable
      24–48 hrStandard Holter10–151–51–5
      3–7 daysPatch/Vest/Belt Recorder/MCT/ELR50–705–105–10 (?)
      1–4 weeksELR/Patch/Vest/Belt Recorder/MCT70–8515–2510–15 (?)
      ≤36 monthsILR80–9030–5015–20 (?)
      MCT, mobile cardiac telemetry; ELR, external loop recorder; ILR, implantable loop recorder.
      Table 3Advantages and major limitations of AECG techniques
      ECG monitoring techniqueAdvantagesLimitations
      Holter monitoring
      • Ability to record and document continuous 3- to 12-lead ECG signal simultaneously with a variety of other biological signals during normal daily activities
      • Familiarity of physicians with analysis software programs and a wide availability of third-party scanning services that outsource the equipment and generate preliminary diagnostic reports
      • Frequent noncompliance with symptom logs and event markers
      • Frequent electrode detachments
      • Signal quality issues due to skin adherence artifacts, wire entanglements, and occasional skin dermatitis caused by electrode gels
      • Absence of real-time data analysis
      • Poor patient acceptance of wire-electrode systems
      Patch ECG monitors
      • Long-term recording of 14 days or longer
      • Excellent patient acceptance
      • Records a limited ECG from closely spaced electrodes comprising a time series of P-, Q-, R-, ST-, and T-wave sequence with lower voltage amplitudes without information on their spatial orientation, thus lacking localization ability of arrhythmia origin
      • Inconsistent optimal ECG signal quality due to varying body types
      External loop recorders
      • Records only selected ECG segments of fixed duration marked as events either automatically or manually by the patient
      • Immediate alarm generation upon event detection
      • Records a single-lead ECG sequence without information on spatial orientation of P, Q, R, ST, and T waves, thus lacking localization ability of arrhythmia origin; P waves may not be visible
      • No capability to continuously document cardiac rhythm
      • Requires patients to wear electrodes continuously during the recording period
      Event recorders
      • Records only selected ECG segments of fixed duration after an event is detected by the patient
      • Immediate alarm generation upon the event detection
      • Well-tolerated by the patient
      • Single-lead devices do not indicate the origin of many arrhythmias
      • No capability to continuously document cardiac rhythm
      • Diagnostic yield of event recorders is highly dependent on patient's ability to recognize correct symptom
      Mobile cardiac telemetry
      • Multilead MCT devices can record pseudo-standard, 3-lead electrocardiogram, hence has a much higher sensitivity and specificity of arrhythmia detection as compared to single-lead devices
      • Can stream the data continuously to caregivers; often combines the functionality of traditional 3-lead Holter event and loop recorder, for example, programmed to autodetect and autosend events at certain time (e.g., 1 every 10 min)
      • Immediate alarm generation upon an event detection without patient interaction or manual activation
      • Electrode-wire MCTs require daily electrode changes, and thus, patient acceptance is reduced for long-term monitoring applications

       3.2. AECG signal acquisition, processing, and interpretation

      There have been major advances in recording and signal processing techniques resulting in enhanced recording fidelity and more sophisticated analysis software (
      • Kennedy H.L.
      The history, science and innovation of Holter technology.
      ).

       3.2.1. Electrodes for AECG applications

      Virtually, all wire and embedded electrodes used by AECG monitoring devices utilize wet gel electrodes. These are nonpolarizable electrode types, with a silver–silver chloride (AgCl) element coated with an ionically active gel. Polarizable silver textrodes (textile electrodes) embedded in the shirt/vest carrier are also now available (
      • Lobodzinski S.S.
      • Laks M.M.
      Comfortable textile-based electrocardiogram systems for very long-term monitoring.
      ,
      • Perez de Isla L.
      • Lennie V.
      • Quezada M.
      • Guinea J.
      • Arce C.
      • Abad P.
      • Zamorano J.
      New generation dynamic, wireless and remote cardiac monitorization platform: A feasibility study.
      ). All ECG monitoring electrodes must comply with ANSI/AAMI EC12:2000 (R 2010) standard and are subject to regulatory oversight (
      Guidance for Industry and Food and Drug Administration Staff
      Class II special controls guidance document: Electrocardiograph electrodes.
      ). AECG signal recording artifacts persist with the newer electrodes, especially those due to motion and impaired skin–electrode interface (see section below) (
      • Keller K.B.
      • Lemberg L.
      Electrocardiographic artifacts.
      ,
      • Knight B.P.
      • Pelosi F.
      • Michaud G.F.
      • Strickberger S.A.
      • Morady F.
      Clinical consequences of electrocardiographic artifact mimicking ventricular tachycardia.
      ,
      • Knight B.P.
      • Pelosi F.
      • Michaud G.F.
      • Strickberger S.A.
      • Morady F.
      Physician interpretation of electrocardiographic artifact that mimics ventricular tachycardia.
      ,
      • Krasnow A.Z.
      • Bloomfield D.K.
      Artifacts in portable electrocardiographic monitoring.
      ,
      • Márquez M.F.
      • Colín L.
      • Guevara M.
      • Iturralde P.
      • Hermosillo A.G.
      Common electrocardiographic artifacts mimicking arrhythmias in ambulatory monitoring.
      ).
      Selection of optimal monitoring electrodes for AECG applications is of critical importance to signal fidelity (
      • Ackermans P.A.
      • Solosko T.A.
      • Spencer E.C.
      • Gehman S.E.
      • Nammi K.
      • Engel J.
      • Russell J.K.
      A user-friendly integrated monitor-adhesive patch for long-term ambulatory electrocardiogram monitoring.
      ,
      • Lobodzinski S.S.
      • Laks M.M.
      New devices for very long-term ECG monitoring.
      ,
      • Locati E.T.
      Advances in modern electrocardiographic equipment for long-term ambulatory monitoring.
      ,
      • Zimetbaum P.
      • Goldman A.
      Ambulatory arrhythmia monitoring: Choosing the right device.
      ,
      • Zimetbaum P.J.
      • Kim K.Y.
      • Josephson M.E.
      • Goldberger A.L.
      • Cohen D.J.
      Diagnostic yield and optimal duration of continuous-loop event monitoring for the diagnosis of palpitations. A cost-effectiveness analysis.
      ). Optimal electrode application includes the following: (1) shaving the skin if necessary; (2) removing dead skin cells by rubbing the area with a rough paper or cloth; (3) using electrodes from air tight packages; and (4) paying attention to expiration dates on the electrodes packages (
      • Kligfield P.
      • Gettes L.S.
      • Bailey J.J.
      • Childers R.
      • Deal B.J.
      • Hancock E.W.
      • Wellens H.
      Recommendations for the standardization and interpretation of the electrocardiogram. Part I: The electrocardiogram and its technology. A scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society.
      ).

       3.2.2. Holter lead configurations

      Ideally, all AECG devices should use 12-lead configuration. Due to technological, patient acceptance, and economic reasons, however, only few AECG monitors have 12-lead system capabilities. A 12-lead Holter lead system shown in Figure 2a uses a quasi-standard Mason-Likar lead system. The arm electrodes are placed in the infraclavicular fossae medial to the deltoid insertions, and the left leg electrode is placed midway between the costal margin and iliac crest in the left anterior axillary line. More recent applications of the Mason-Likar monitoring position place the arm electrodes over the outer clavicles and the right leg electrode (body potential reference) at the sternum. The precordial electrodes are placed in the standard positions (
      • Drew B.J.
      • Finlay D.D.
      Standardization of reduced and optimal lead sets for continuous electrocardiogram monitoring: Where do we stand?.
      ,
      • Welinder A.
      • Wagner G.S.
      • Maynard C.
      • Pahlm O.
      Differences in QRS axis measurements, classification of inferior myocardial infarction, and noise tolerance for 12-lead electrocardiograms acquired from monitoring electrode positions compared to standard locations.
      ). When 12-lead AECG monitors are not available, a “pseudo-standard” lead system may be used. These are usually either 2-channel/7-electrode frontal plane configurations.
      Figure thumbnail gr2
      Figure 2Holter lead configurations. (A) Mason-Likar 12-lead system for continuous ECG monitoring. Electrode placements are as follows: RA: 2nd intercostal space right side midclavicular, LA 2nd intercostal space left side midclavicular, LL below 8th intercostal left side midclavicular line, RL: upper sternum, V1: 4th right intercostal space at the sternal border, V2: 4th left intercostal space at the sternal border, V3: between V2 and V4, V4: 5th left intercostal space at the midclavicular line, V5: 5th left intercostal space at the anterior axillary line, V6: 5th left intercostal space at the midaxillary line; (B) EASI reduced leads system. EASI is a reduced lead system suitable for continuous ECG monitoring. It is an alternative to both the commonly used 5-electrode monitoring system and the traditional 10-electrode Mason-Likar 12-lead ECG system. The EASI lead configuration enables continuous reconstructed 12-lead ECG ambulatory monitoring using only five electrodes. The EASI 12-lead ECG is derived from a set of four recording electrodes and one reference electrode. The placement of these leads is as follows: E: lower extreme of the sternum, A: left mid-axillary line, same transverse line as E, S: sternal manubrium, I: right mid-axillary line, same transverse line as E, R: fifth electrode is the body potential reference and can be placed anywhere on the torso.
      The EASI lead system (Figure 2b) is a reduced 5-electrode system that uses the E, A, and I electrodes from the Frank lead system and adds an “S” electrode at the top of the mid sternum, along with a body reference electrode to provide orthogonally oriented signals. This eliminates the need to determine intercostal spaces and avoids the breast. EASI lead system makes use of the transformation coefficient matrix that produce synthesized 12-lead ECGs. EASI is well suited for AECG applications because of the absence of limb electrodes, which usually produce signal artifacts in active subjects.
      Most patch ECG monitors, ELR, event recorders, and MCT monitors available today feature only a single lead derived from two closely spaced embedded or wired electrodes (
      • Lobodzinski S.S.
      ECG patch monitors for assessment of cardiac rhythm abnormalities.
      ,
      • Lobodzinski S.S.
      • Laks M.M.
      New devices for very long-term ECG monitoring.
      ). A variety of single-lead configurations are only possible in wire-electrode systems, the most common being a chest-modified V5 (CM5), a chest-modified V3 (CM3), and a modified inferior lead. Specific lead configurations can be chosen in specific situations (e.g., in case of a patient undergoing AECG monitoring for ischemia, the AECG lead configuration should be chosen to mimic those leads with the greatest ST-segment change during exercise).
      Ambulatory ECGs recorded with torso placement of the extremity electrodes cannot be considered equivalent to standard ECGs for all purposes and should not be used interchangeably with standard ECGs for serial comparison (
      • Papouchado M.
      • Walker P.R.
      • James M.A.
      • Clarke L.M.
      Fundamental differences between the standard 12-lead electrocardiograph and the modified (Mason-Likar) exercise lead system.
      ). For example, a 12-lead ECG is the diagnostic test of choice for long QT syndrome (LQTS), rather than an AECG.

       3.2.3. AECG processing

      All modern AECG instrumentation today is digital and subject to regulatory guidelines (
      • Guidance for Industry and Food and Drug Administration Staff
      Class II Special controls guidance document: Arrhythmia detector and alarm.
      ). The front end is typically a highly integrated system on the chip (SoC) responsible for surge protection (defibrillator shock), analog-to-digital conversion, digital filtering, and calibration. The processing flow of the AECG signal starts with the biopotential signal acquisition front-end subsystem of the monitor. Common-mode rejection ratio, or CMRR, is one of the most important performance parameters for ECG system applications and is subject to regulatory approval. A driven right leg circuit or “DRL” circuit is an electric circuit that is added to ECG signal amplifiers to reduce common-mode interference. SoC provide multichannel, simultaneous sampling, 24-bit, delta-sigma (ΔΣ) analog-to-digital converters (ADCs) with built-in programmable gain amplifiers capable of resolving signals as small as pico volts. Unfortunately, the patient's body can also act as an antenna which picks up electromagnetic interference, especially 50/60 Hz noise from electrical power lines. This interference signal induces voltages much greater than the ECG signal itself, thus making it very challenging to measure. right leg driver circuitry is used to eliminate interference noise by actively canceling the interference signal (
      • Winter B.B.
      • Webster J.G.
      Driven-right-leg circuit design.
      ).
      The AECG digital signal must then be amplified and low-pass filtered in SoC to prevent aliasing errors. Next, the digital AECG is band-pass and notch filtered to eliminate or suppress low-frequency noise caused by baseline wander, respiration, and higher frequency noise cased by muscle tremors and induced electromagnetic interference. Once amplified, filtered, and smoothed, the analysis of the AECG can proceed. The end result of this operation is the delineation of the AECG into P, QRS, and T waveforms. Global waveform measurements, such as duration, amplitudes, ratios, are derived from individual lead data or from mathematical combinations of simultaneously acquired individual lead data and stored in the measurement matrix. The accuracy of the waveform classification highly depends on the redundancy of the information contained in a multilead system. Generally speaking, the higher the number of the leads the higher the complex detection precision.

       3.2.4. Mobile cardiac telemetry ECG data transmission

      The MCT devices use either packet-oriented mobile data service on the 2G and 3G cellular communication system (GPRS) or a combination of Bluetooth with a Wi-Fi 802.11 b/g/n relay station (
      • Engel J.M.
      • Chakravarthy N.
      • Katra R.P.
      • Mazar S.
      • Libbus I.
      • Chavan A.
      Estimation of patient compliance in application of adherent mobile cardiac telemetry device.
      ). GPRS uses powerful algorithms and encryption techniques on security controls that include subscriber identity confidentiality, subscriber identity authentication, user data confidentiality on physical connections, connectionless user data confidentiality, and signaling information element. The MCTs that use Bluetooth security feature transmit data via relay (smartphone, tablet, and dedicated transmission device) to the remote reading centers. The newly announced Smart Bluetooth low-energy protocol used by the latest MCT devices also features robust security measures. The weakest link in relay type of AECG data transmission is the HTTPS data transmission protocol widely used over the Internet.

       3.2.5. AECG analysis and interpretation

      Many ECG processing algorithms exist today. Most are proprietary, and very few data are available regarding their documented clinical accuracy. The developers usually use the annotated MIT-BIH ECG and arrhythmia databases available on physionet.org to tune their algorithms (
      • George B.M.
      • Roger G.M.
      The impact of the MIT-BIH arrhythmia database.
      ). All AECG data are processed in an off-line fashion using specialized computer workstations, whereas MCT and patch ECG data are always processed in dedicated reading centers. Processing algorithms detect and document abnormal rhythms or conduction abnormalities, and provide a quantitative analysis of supraventricular and ventricular rhythm disorders (the so-called “arrhythmic burden”). Additional algorithms can also analyze multiple parameters of the ECG signals, such as assessment of ST-segment shifts, heart rate variability (HRV), QT dynamics and T-wave variability, T-wave alternans (TWA), heart rate turbulence (HRT) (
      • Hoefman E.
      • Van Weert H.C.
      • Reitsma J.B.
      • Koster R.W.
      • Bindels P.J.
      Diagnostic yield of patient-activated loop recorders for detecting heart rhythm abnormalities in general practice: A randomized clinical trial.
      ,
      • Joshi A.K.
      • Kowey P.R.
      • Prystowsky E.N.
      • Benditt D.G.
      • Cannom D.S.
      • Pratt C.M.
      • Sangrigoli R.M.
      First experience with a Mobile Cardiac Outpatient Telemetry (MCT) system for the diagnosis and management of cardiac arrhythmia.
      ,
      • Salleh S.H.
      • Hussain H.S.
      • Swee T.T.
      • Ting C.M.
      • Noor A.M.
      • Pipatsart S.
      • Yupapin P.P.
      Acoustic cardiac signals analysis: A Kalman filter-based approach.
      ).

       3.2.6. Pitfalls in the interpretation of arrhythmias detected by AECG and MCT

      Two main categories of ECG artifacts are recognized. One group includes those related to body movement, temporary impairment of skin–electrode contact, loose electrode connections, dysfunctional leads, skeletal myopotentials, and ambient noise. These can generate deflections that can simulate a variety of arrhythmias and are thus termed, pseudo-atrial arrhythmias, for example, atrial flutter or fibrillation (Figure 3a), or pseudo-ventricular tachyarrhythmia (Figure 3b,c). A second group of artifacts is probably related to intermittent impairment of electrode contact or recorder problems in older recording systems that can result in tape slowing or intermittent stoppage (
      • Krasnow A.Z.
      • Bloomfield D.K.
      Artifacts in portable electrocardiographic monitoring.
      ,
      • Márquez M.F.
      • Colín L.
      • Guevara M.
      • Iturralde P.
      • Hermosillo A.G.
      Common electrocardiographic artifacts mimicking arrhythmias in ambulatory monitoring.
      ). These artifacts result in pseudo-pauses that can simulate sinus arrest, pacemaker malfunction, or high-degree atrioventricular conduction block. The majority of artifacts can be recognized from simultaneous multichannel ECG.
      Figure thumbnail gr3
      Figure 3Examples of ECG artifacts (A) The bottom channel shows recording artifact that may simulate atrial flutter/fibrillation. However, careful analysis of the upper channel shows sinus rhythm with clear P waves. The presence of an irregular rhythm secondary to both sinus arrhythmia and occasional premature atrial beats adds to difficulty in making the correct diagnosis from the recording in the bottom channel alone. Figures (B and C) are two distinct examples of artifacts from the same Holter recording that may simulate ventricular tachyarrhythmia. In both tracings, the artifacts are more prominent in one of the two illustrated channels but not the other, making correct interpretation feasible. Normal QRS complexes are marked by arrows at the channel with prominent artifacts.
      Reproduced with permission from
      • El-Sherif N.
      • Turitto G.
      Ambulatory electrocardiographic monitoring between artifacts and misinterpretation, management errors of commission and errors of omission.
      .
      In contrast to the role of the more common AECG artifacts, failure by the technician or clinician to recognize a genuine arrhythmia episode in the ECG recording may lead to potentially more serious implications (
      • El-Sherif N.
      • Turitto G.
      Ambulatory electrocardiographic monitoring between artifacts and misinterpretation, management errors of commission and errors of omission.
      ). This problem is significantly more common on the hospital cardiac telemetry service and highlights the need of improved training in the detection and interpretation of AECG of the technical and clinical staff who make up this service (See Section 6).
      The clinical implication of misinterpretation of AECG recordings could result in errors of commission and errors of omission. Errors of commission include, but are not confined to, recommending the wrong medication or potentially harmful and unnecessary interventional procedures such as cardiac catheterization, electrophysiological study, or implantation of arrhythmia devices (
      • Krasnow A.Z.
      • Bloomfield D.K.
      Artifacts in portable electrocardiographic monitoring.
      ). Errors of omission include failure to properly address patients with potentially serious arrhythmic events.

      4. Section 2: Clinical Indications—Diagnostics

       4.1. Syncope

      Syncope (loss of consciousness from either sudden or gradual but persistent decrease of blood flow to the brain as a consequence of low cardiac output) may be due to primary electrical problems (bradycardia/tachycardia) or hemodynamic causes. The role of the AECG is to identify (
      • Watanabe E.
      • Tanabe T.
      • Osaka M.
      • Chishaki A.
      • Takase B.
      • Niwano S.
      • Aizawa Y.
      Sudden cardiac arrest recorded during Holter monitoring: Prevalence, antecedent electrical events and outcomes.
      ) bradyarrhythmias (e.g., sinus pauses, periods of atrioventricular [AV] block), or tachyarrhythmias (e.g., sustained VT).
      Several guidelines, scores, and recommendations for the diagnosis and management of patients with syncope have been published in the last decade (
      • Ammirati F.
      • Colivicchi F.
      • Santini M.
      Diagnosing syncope in the clinical practice. Implementation of a simplified diagnostic algorithm in a multicentre prospective trial—the OESIL 2 Study (Osservatorio Epidemioologico dell Sincope nel Lazio).
      ,
      • Baranchuk A.
      • Morgan S.
      • Krahn A.
      • Bentley C.
      • Ribas S.
      • Guzman J.C.
      • Morillo C.A.
      Registry on the evaluation of syncope assessment strategy in the emergency room (RESASTER Study).
      ,
      • Brignole M.
      • Alboni P.
      • Benditt D.
      • Bergfeldt L.
      • Blanc J.J.
      • Bloch Thomsen P.E.
      • Wieling W.
      Task Force on Syncope, European Society of Cardiology. Guidelines on management (diagnosis and treatment) of syncope.
      ,
      • Cerrone M.
      • Priori P.G.
      Routine electrocardiogram and medical history in syncope: A simple approach can identify most high-risk patients.
      ,
      • Colivicci F.
      • Ammirati F.
      • Melina D.
      • Guido V.
      • Imperoli G.
      • Santini M.
      OESIL (Osservatorio Epidemiologico sulla Sincope nel Lazio) Study Investigators
      Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: The OESIL risk score.
      ,
      • Locati E.T.
      • Vecchi A.M.
      • Vargiu S.
      • Cattafi G.
      • Lunati M.
      Role of extended external loop recorders for the diagnosis of unexplained syncope, pre-syncope, and sustained palpitations.
      ,
      • Morillo C.A.
      • Baranchuk A.
      Current management of syncope: Alternatives of treatment.
      ,
      • Moya A.
      • Sutton R.
      • Ammirati F.
      • Blanc J.J.
      • Brignole M.
      • Dahm J.B.
      • Wieling W.
      Guidelines for the diagnosis and management of syncope (version 2009).
      ,
      • Sheldon R.
      • Rose S.
      • Connolly S.
      • Ritchie D.
      • Koshman M.
      • Fenneaux M.
      Diagnostic criteria for vasovagal syncope based on a quantitative history.
      ). Most provide recommendations on the need for hospital admission and the nature of further diagnostic workup to identify or exclude high-risk causes of syncope. A significant number of low-risk patients are unnecessarily admitted for further investigation, and a role for outpatient use of AECG can be offered as an alternative.
      Symptom/rhythm correlation remains the cornerstone of the diagnostic efforts in syncope to confirm the involvement of the cardiac electrical system in the origin of syncope (
      • Morillo C.A.
      • Baranchuk A.
      Current management of syncope: Alternatives of treatment.
      ). The choice of monitoring modality depends on the frequency of events. Sometimes a single surface 12-lead ECG may be enough to establish the connection between the symptom and the cardiac rhythm (e.g., complete heart block); however, more often extended monitoring is necessary as at the time of the evaluation the cause of syncope remains elusive because of its transient and intermittent nature (
      • Baron-Esquivias G.
      • Martínez-Alday J.
      • Martín A.
      • Moya A.
      • García-Civera R.
      • Paz López-Chicharro M.
      • Laguna P.
      Epidemiological characteristics and diagnostic approach in patients admitted to the emergency room for transient loss of consciousness: Group for Syncope Study in the Emergency Room (GESINUR) study.
      ). The pediatric population represents a specific challenge, especially the very young who may be unable to verbalize symptoms or comply with complex instructions; these young patients may require more automated recording systems tailored to the individual circumstance.

       4.1.1. Bradyarrhythmias that can be detected by AECG

      • 1.
        Transient and paroxysmal high-degree AV block: AECG allows detection of a sudden interruption of AV conduction without slowing of the sinus discharge. The latter would suggest a vagal or neurocardiogenic mechanism rather than primary disease of the electrical conductive system (and suggest avoidance of pacemaker implantation).
      • 2.
        Sinus node dysfunction (
        • Dąbrowski A.
        • Piotrowicz R.
        Circadian rhythm of sinoatrial conduction time. A new approach to the study of the sinoatrial node.
        ,
        • Makowski K.
        • Kramarz E.
        Holter monitoring, sinoatrial conduction time, prognosis.
        ): Defects of sinus automaticity include sinoatrial block, sinus bradycardia, tachy/brady syndrome, sinus pauses, and postconversion asystole (usually associated with atrial fibrillation [AF]). It is strongly recommended to establish symptom/rhythm correlation, as formalized cutoffs are arbitrary although a sinus rate <40 bpm is considered potentially causative in a symptomatic patient (
        • Epstein A.E.
        • DiMarco J.P.
        • Ellenbogen K.A.
        • Estes 3rd, N.A.
        • Freedman R.A.
        • Gettes L.S.
        Heart Rhythm Society
        2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
        ). A variety of AECG recorders can indicate whether sinus node competency is inadequate to match the metabolic demands of the individual patient and produce symptoms. The specifics of monitor selection depend on the frequency and nature of symptoms.

       4.1.2. Tachyarrhythmias that can be detected by ambulatory telemetry

      • 1.
        Supraventricular tachycardias are a rare cause of syncope, with exceptions in the setting of heart failure or cardiomyopathy, or during postconversion sinus pause. They are diagnosed by the presence of a narrow complex rhythm with QRS complex similar to that of sinus rhythm in most cases. A variety of mechanisms exist and some have unique patterns and initiation sequences. In some patients, supraventricular tachyarrhythmias produce QRS aberration and present as a wide complex tachycardia. As AECGs do not usually have the full array of ECG leads, the aberrantly conducted rhythm may be challenging to identify as supraventricular in origin.
      • 2.
        Ventricular tachyarrhythmias include ventricular tachycardias (monomorphic and polymorphic), ventricular fibrillation, and torsade de pointes. AECG monitoring is only one component of the investigation and most useful if recorded during symptoms. Many patients with depressed left ventricular function will be candidates for implantable cardioverter defibrillator (ICD) based on left ventricular ejection fraction (LVEF), and others may require electrophysiological study for programmed stimulation to elicit VT.
      An AECG monitor is used in many patients who have unexplained syncope. The strategy of AECG recording is based on two objectives: (1) capture of a serious arrhythmic event that is sufficient to explain syncope, can imply the possibility of even more serious arrhythmic events, or is in and of itself sufficient to warrant treatment or intervention; and (2) correlate the presence of recurrent symptoms with an arrhythmic event that can guide therapy, or equally importantly, demonstrate the absence of arrhythmia during recurrent symptoms, effectively excluding an arrhythmic basis for syncope. For example, the first objective may be met when periods of higher grade AV block are observed, particularly in setting of bundle branch block (e.g., Type II 2o AV block or transient 3o AV block). When pursuing the second objective, one study of short-term Holter monitoring found that symptoms correlated with a documented arrhythmia in 4% and occurred without an arrhythmia on the monitor in 17% (
      • Morillo C.A.
      • Baranchuk A.
      Current management of syncope: Alternatives of treatment.
      ).
      The type of recorder and the duration of recording should be tailored to the individual patient's history, but in general, the diagnostic yield is limited and dependent on the frequency of clinical symptoms. Extended recordings may improve diagnostic yield. In 1 trial, the overall probability of obtaining a symptom–rhythm correlation increased from 22% to 56% for 48-hr Holters compared to 1 month of ECG loop recording (
      • Sivakumaran S.
      • Krahn A.D.
      • Klein G.J.
      • Finan J.
      • Yee R.
      • Renner S.
      • Skanes A.C.
      A prospective randomized comparison of loop recorders versus Holter monitors in patients with syncope or presyncope.
      ). In another study, the median time for recording a symptom–rhythm correlation was 16 days for patients assigned a loop recorder as their first diagnostic strategy and symptom–rhythm correlation was obtained in 87% of patients by 1 month of monitoring (
      • Bass E.B.
      • Curtis El
      • Arena V.C.
      • Hanusa B.H.
      • Cecchetti A.
      • Karpf M.
      • Kapoor W.N.
      The duration of Holter monitoring in patients with syncope. Is 24 hours enough?.
      ). Much longer monitoring using ILRs can further improve the diagnostic yield for syncope, as high as 85% in some studies (
      • Cotter P.E.
      • Martin P.J.
      • Ring L.
      • Warburton E.A.
      • Belham M.
      • Pugh P.J.
      Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke.
      ).
      Although exercise-induced arrhythmias are typically worked up via an exercise treadmill examination, there may be value in using AECG recording, especially for adolescents. This may facilitate recordings during more natural activities and also stimulate levels of exertion not achieved in an artificial environment, enhancing symptom–rhythm correlation.

       4.2. Palpitations

      Palpitations are the most frequent indication for AECG, and one of the main reasons why AECG was originally developed. Up to 20% of outpatients present with palpitations and most of the cases have benign causes (
      • Kroenke K.
      • Arrington M.E.
      • Mangelsdorff A.D.
      The prevalence of symptoms in medical outpatients and the adequacy of therapy.
      ). Although a detailed history, physical examination, and 12-lead ECG are sufficient to make a definitive diagnosis in up to one-third of patients with palpitations, in the remainder AECG is the most cost-effective clinical tool (
      • Weber B.E.
      • Kapoor W.N.
      Evaluation and outcomes of patients with palpitations.
      ).
      Ambulatory ECG monitoring for symptom–ECG correlation is indicated for the following groups of patients with unexplained palpitations: (1) when history, physical examination, and 12-lead ECG suggest a possibility of arrhythmia; (2) in the setting of diagnosed structural heart disease, family history of sudden cardiac death (SCD), or inherited channelopathy with known risk of arrhythmia; (3) when patients need reassurance and specific explanation of their symptoms, and (4) when symptoms warrant therapy and specifics of treatment are dependent on a formal arrhythmic diagnosis (e.g., ablation, antiarrhythmic therapy).
      Ambulatory ECG monitoring is the key tool for the diagnosis of unexplained, well-tolerated recurrent palpitations. Clinical presentation and frequency of palpitations should be taken into consideration when selecting the device (
      • Crawford M.H.
      • Bernstein S.J.
      • Deedwania P.C.
      • DiMarco J.P.
      • Ferrick K.J.
      • Garson Jr., A.
      • Smith Jr., S.C.
      ACC/AHA guidelines for ambulatory electrocardiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography). Developed in collaboration with the North American Society for Pacing and Electrophysiology.
      ,
      • Mittal S.
      The evaluation of the patient with unexplained palpitations: Maximizing diagnostic yield while minimizing unnecessary frustration.
      ,
      • Raviele A.
      • Giada F.
      • Bergfeldt L.
      • Blanc J.J.
      • Blomstrom-Lundqvist C.
      • Mont L.
      • Shah D.C.
      European Heart Rhythm Association
      Management of patients with palpitation: A position paper from the European Heart Rhythm Association.
      ). Traditional AECG monitor (24–48 hr) is indicated for patients who experience frequent palpitations every day, or can reliably reproduce symptoms (e.g., positional or exertional palpitations). It is important for a patient to keep a diary recording the time of palpitations. The relevance of identified spontaneous arrhythmias to the palpitations is variable and could be low (
      • Lok N.S.
      • Lau C.P.
      Prevalence of palpitations, cardiac arrhythmias and their associated risk factors in ambulant elderly.
      ,
      • Zeldis S.M.
      • Levine B.J.
      • Michelson E.L.
      • Morganroth J.
      Cardiovascular complaints. Correlation with cardiac arrhythmias on 24-hour electrocardiographic monitoring.
      ). Loop event recorders and interactive ECG applications that save and transmit ECG only when the patient activates the monitor are suitable for patients with infrequent and unpredictable palpitations. Such devices provide better correlation with symptoms, but require that the patient be vigilant and capable of activating the recording in time. Continuous-loop recorders provided higher diagnostic yield, as compared to 24-hr Holter, and have proved to be more cost-effective (
      • Fogel R.I.
      • Evans J.J.
      • Prystowsky E.N.
      Utility and cost of event recorders in the diagnosis of palpitations, presyncope, and syncope.
      ). It has been shown that 2 weeks of ECG monitoring provide the best balance between diagnostic yield and associated cost (
      • Zimetbaum P.J.
      • Kim K.Y.
      • Josephson M.E.
      • Goldberger A.L.
      • Cohen D.J.
      Diagnostic yield and optimal duration of continuous-loop event monitoring for the diagnosis of palpitations. A cost-effectiveness analysis.
      ). The diagnostic yield of AECG directly correlates with the duration of AECG monitoring and depends on the percentage of “accurate reporters” in the studied population. Typically, diagnosed rhythms reflect prevalence of arrhythmias in the studied populations (Table 2).

       4.3. Chest pain and coronary ischemia

      Ambulatory ECG monitoring can be utilized to diagnose the etiology of chest pain (both atherosclerotic coronary artery disease and Prinzmetal's variant angina), identify episodes of atypical chest pain that do not have an apparent manifestation on the surface ECG, and assess the magnitude of “ischemic burden,” the product of duration of ischemia and the magnitude of ST-segment depression. The majority of episodes of ambulatory ischemia in patients with coronary disease are asymptomatic, and therefore objective ECG monitoring, such as with the AECG, can be used to identify the severity of ischemia during daily activities (
      • Birnbaum Y.
      • Nikus K.
      • Kligfield P.
      • Fiol M.
      • Barrabés J.A.
      • Sionis A.
      • de Bayès Luna A.
      The role of the ECG in diagnosis, risk estimation, and catheterization laboratory activation in patients with acute coronary syndromes: A consensus document.
      ).
      For a diagnosis of ischemia, ST-segment depression of at least 0.5–1.0 mV (0.5–1.0 mm) lasting for at least 1 min before returning to normal should be seen (
      • Conti C.R.
      • Bavry A.A.
      • Petersen J.W.
      Silent ischemia: Clinical relevance.
      ). Reported rates of ST-depression sensitivity (62%) and specificity (61%) as detected by continuous ECG in patients with angiographically defined chest pain and known coronary artery disease are similar to those derived from an exercise treadmill test (67% and 65%, respectively) using similar lead positions. With AECG monitoring, nearly one-half of patients with stable coronary artery disease exhibit transient ST-segment depressions that likely represent ischemic events (
      • Pepine C.J.
      • Geller N.L.
      • Knatterud G.L.
      • Bourassa M.G.
      • Chaitman B.R.
      • Davies R.F.
      • Conti C.R.
      The Asymptomatic Cardiac Ischemia Pilot (ACIP) study: Design of a randomized clinical trial, baseline data and implications for a long-term outcome trial.
      ,
      • Smith Jr., S.C.
      • Amsterdam E.
      • Balady G.J.
      • Bonow R.O.
      • Fletcher G.F.
      • Froelicher V.
      • Wenger N.K.
      Prevention Conference V: Beyond secondary prevention: Identifying the high-risk patient for primary prevention: Tests for silent and inducible ischemia: Writing Group II.
      ). This has important prognostic information, potentially beyond the findings obtained during an exercise treadmill test. In one study, after multivariable adjustment, only ST-segment depression during AECG monitoring, and not ST-segment depression during exercise testing, significantly predicted worse outcomes (
      • Rocco M.B.
      • Nabel E.G.
      • Campbell S.
      • Goldman L.
      • Barry J.
      • Mead K.
      • Selwyn A.P.
      Prognostic importance of myocardial ischemia detected by ambulatory monitoring in patients with stable coronary artery disease.
      ). In patients with unstable coronary syndromes, silent ischemia can predict both short-term and long-term risk (
      • Gibson C.M.
      • Pride Y.B.
      • Buros J.L.
      • Ciaglo L.N.
      • Morrow D.A.
      • Scirica B.M.
      • Stone P.H.
      Timing and duration of myocardial ischemia on holter monitoring following percutaneous coronary intervention and their association with clinical outcomes (a protect-timi 30 substudy analysis).
      ,
      • Gottlieb S.O.
      • Weisfeldt M.L.
      • Ouyang P.
      • Mellits E.D.
      • Gerstenblith G.
      Silent ischemia predicts infarction and death during 2 year follow-up of unstable angina.
      ,
      • Langer A.
      • Singh N.
      • Freeman M.R.
      • Tibshirani R.
      • Armstrong P.W.
      Detection of silent ischemia adds to the prognostic value of coronary anatomy and left ventricular function in predicting outcome in unstable angina patients.
      ,
      • Patel D.J.
      • Knight C.J.
      • Holdright D.R.
      • Mulcahy D.
      • Clarke D.
      • Wright C.
      • Fox K.M.
      Pathophysiology of transient myocardial ischemia in acute coronary syndromes. Characterization by continuous ST-segment monitoring.
      ,
      • Scirica B.M.
      • Morrow D.A.
      • Budaj A.
      • Dalby A.J.
      • Mohanavelu S.
      • Qin J.
      • Braunwald E.
      Ischemia detected on continuous electrocardiography after acute coronary syndrome: Observations from the merlin-timi 36 (metabolic efficiency with ranolazine for less ischemia in non-st-elevation acute coronary syndrome-thrombolysis in myocardial infarction 36) trial.
      ).
      Ambulatory ECG monitoring has also been utilized to diagnose and manage patients with the rare syndrome of Prinzmetal's variant angina, but confirmation of adequate therapeutic prevention of vasospasm episodes has been primarily based on provocative testing in the cardiac catheterization laboratory (
      • Bayés de Luna A.
      • Cygankiewicz I.
      • Baranchuk A.
      • Fiol M.
      • Birnbaum Y.
      • Nikus K.
      • Breithardt G.
      Prinzmetal angina: ECG changes and clinical considerations: A consensus paper.
      ,
      • Waters D.D.
      • Szlachcic J.
      • Theroux P.
      • Dauwe F.
      • Mizgala H.F.
      Ergonovine testing to detect spontaneous remissions of variant angina during long-term treatment with calcium antagonist drugs.
      ).
      In patients suffering ST elevation myocardial infarction (STEMI), early reperfusion via percutaneous coronary intervention (PCI) remains the critical therapeutic intervention. As PCI resources are only available in specific institutions, prehospital diagnosis has specific practical advantages: directing emergency transport to the optimal facility, bypassing the emergency department, and preparation at the receiving facility for emergent PCI and associated treatment. The emergency transport system must be capable of recording a 12-lead ECG and transmitting the ECG to a center that can provide skilled confident interpretation. The Danish health system has formally implemented such a system for several years, processing about 4,000 ECGs per year, and observed that 81% of prehospital diagnoses of STEMI underwent emergent PCI resulting in an acceptable low “false-positive” rate (
      • Clemmensen P.
      • Schoos M.M.
      • Lindholm M.G.
      • Rasmussen L.S.
      • Steinmetz J.
      • Hesselfeldt R.
      • Sejersten M.
      Pre-hospital diagnosis and transfer of patients with acute myocardial infarction—A decade long experience from one of Europe's largest STEMI networks.
      ). This rapid triage system has been associated with a decline in 30-day mortality rates, confirming technical feasibility and suggesting measurable clinical impact.

       4.4. Special considerations for pediatric patients

      AECG in pediatric patients bears special consideration. Indications are similar to adult patients, largely predicated upon symptom frequency and duration, and also for risk stratification and assessing treatment efficacy.
      Palpitations are a common presenting symptom. Arrhythmia correlation during AEGM was noted in 10%–15% of pediatric patients experiencing palpitations. Conversely, sinus tachycardia is identified in nearly 50% of patients with the same symptoms (
      • Dick 2nd, M.
      • McFadden D.
      • Crowley D.
      • Rosenthal A.
      Diagnosis and management of cardiac rhythm disorders by transtelephonic electrocardiography in infants and children.
      ,
      • Fyfe D.A.
      • Holmes Jr., D.R.
      • Neubauer S.A.
      • Feldt R.H.
      Transtelephonic monitoring in pediatric patients with clinically suspected arrhythmias.
      ,
      • Goldstein M.A.
      • Hesslein P.
      • Dunnigan A.
      Efficacy of transtelephonic electrocardiographic monitoring in pediatric patients.
      ,
      • Karpawich P.P.
      • Cavitt D.L.
      • Sugalski J.S.
      Ambulatory arrhythmia screening in symptomatic children and young adults: Comparative effectiveness of holter and telephone event recordings.
      ). In one single-center experience of 495 pediatric patients, transtelephonic electrocardiographic event monitors (TTMs) yielded a useful diagnosis in 48% (
      • Saarel E.V.
      • Stefanelli C.B.
      • Fischbach P.S.
      • Serwer G.A.
      • Rosenthal A.
      • Dick 2nd, M.
      Transtelephonic electrocardiographic monitors for evaluation of children and adolescents with suspected arrhythmias.
      ). Conversely, >50% patients in this study failed to transmit a single, legible ECG while symptomatic, highlighting the limitation of patient-activated equipment in the pediatric population. This is compounded by age-related compliance: Most young children (<5 years) are unable to comply with event triggered monitoring. Clinicians have circumvented this issue by allowing parents, caregivers, or even teachers to provide the activation. Of course, in time-sensitive events, this is not always plausible which remains a major limitation of this equipment.
      The evaluation of syncope creates a diagnostic challenge with patient-activated AECG. Temporary loss of consciousness precludes patient triggered activation. As such, clinicians recommend outpatient cardiac telemetry with continuous recording independent of patient activation. In some circumstances, ILRs may ensure capture of syncopal events. A cardiac cause of chest pain is extremely unlikely in the pediatric population. In a large prospective study, <5% of patients were identified as having a cardiac cause of their chest pain (
      • Selbst S.M.
      • Ruddy R.M.
      • Clark B.J.
      • Henretig F.M.
      • Santulli Jr., T.
      Pediatric chest pain: A prospective study.
      ). Therefore, AECG has low diagnostic yield but has utility to exclude cardiac- or rhythm-related etiologies to symptoms as a means of providing reassurance to patients and families.
      AECG can be useful for risk assessment. In asymptomatic patients with Wolff–Parkinson–White, recent guidelines favor exercise stress testing to detect beat-to-beat loss of preexcitation (
      • Tanel R.E.
      Pediatric and Congenital Electrophysiology Society (PACES), Heart Rhythm Society (HRS), American College of Cardiology Foundation (ACCF), American Heart Association (AHA), American Academy of Pediatrics (AAP), Canadian Heart Rhythm Society (CHRS)
      PACES/HRS expert consensus statement on the management of the asymptomatic young patient with a wolff-parkinson-white (WPW, ventricular preexcitation) electrocardiographic pattern: Developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), the American Academy of Pediatrics (AAP), and the Canadian Heart Rhythm Society (CHRS).
      ). This may be accomplished with AECG though typically lead analysis and electrogram quality are inferior to those obtained during 12-lead rhythm strip evaluation during formal stress testing. AECG is a relatively routine portion of serial evaluation in pediatric patients with congenital heart disease (CHD). For example, AECG is a class I recommendation for patients with repaired CHDs or for patients with significant residual, hemodynamic abnormalities (
      • Crawford M.H.
      • Bernstein S.J.
      • Deedwania P.C.
      • DiMarco J.P.
      • Ferrick K.J.
      • Garson Jr., A.
      • Smith Jr., S.C.
      ACC/AHA guidelines for ambulatory electrocardiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography). Developed in collaboration with the North American Society for Pacing and Electrophysiology.
      ). In adult patients with CHDs, AECG is considered as a class IIa for monitoring of arrhythmias and/or conduction disturbances (
      • Baumgartner H.
      • Bonhoeffer P.
      • De Groot N.M.
      • de Haan F.
      • Deanfield J.E.
      • Galie N.
      ESC Committee for Practice Guidelines (CPG)
      ESC Guidelines for the management of grown-up congenital heart disease (new version 2010).
      ,
      • Khairy P.
      • Van Hare G.F.
      • Balaji S.
      • Berul C.I.
      • Cecchin F.
      • Cohen M.I.
      • Warnes C.A.
      PACES/HRS Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease: Developed in partnership between the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS). Endorsed by the governing bodies of PACES, HRS, the American College of Cardiology (ACC), the American Heart Association (AHA), the European Heart Rhythm Association (EHRA), the Canadian Heart Rhythm Society (CHRS), and the International Society for Adult Congenital Heart Disease (ISACHD).
      ). The finding of nonsustained ventricular tachycardia is considered a significant risk factor for sudden death in patients with hypertrophic cardiomyopathy (HCM) (
      • Elliott P.M.
      • Anastasakis A.
      • Borger M.A.
      • Borggrefe M.
      • Cecchi F.
      • Charron P.
      • Watkins H.
      2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).
      ,
      • Gersh B.J.
      • Maron B.J.
      • Bonow R.O.
      • Dearani J.A.
      • Fifer M.A.
      • Link M.S.
      American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
      2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      ). Indications for pacemaker implantations in patients with congenital complete heart block are largely predicated on the presence of prolonged pauses, low average heart rates, or complex ventricular ectopy on Holter monitoring (
      • Epstein A.E.
      • DiMarco J.P.
      • Ellenbogen K.A.
      • Estes 3rd, N.A.
      • Freedman R.A.
      • Gettes L.S.
      Heart Rhythm Society
      2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      ).
      Despite important limitations in the pediatric patient, AECG has become a standard diagnostic tool for rhythm assessment. As technology improves and devices become more compatible and less cumbersome for our “smaller” population (e.g., patch technologies with continuous monitoring), the utilization of these devices and their diagnostic power will undoubtedly increase.

      5. Section 3: Clinical Indications—Prognosis and Risk Stratification

      Ambulatory ECG detection of transient arrhythmias, electrical pertubations, or autonomic disturbances has been used for risk stratification although its value varies according to clinical context. In the absence of structural and/or electrical heart disease, the prognostic value of these recordings is generally weak or absent.

       5.1. Ischemic heart disease and postinfarction patients

      Premature ventricular complexes (PVCs) and nonsustained (NS) VT have long been associated with increased risk in patients recovering from acute MI. The nature of MI care has changed dramatically in recent years, so more contemporary analyses are germaine to guiding modern care. In patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), the development of NSVT (≥3 beats, ≥100 bpm) beyond the first 48 hr after admission signifies the presence of increased mortality risk. Continuous 7-day ECG monitoring in NSTE-ACS patients in the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation ACS-Thrombolysis In Myocardial Infarction (MERLIN-TIMI) 36 trial recorded at least one episode of NSVT in more than half of the patients in the overall cohort. Moreover, both short and longer NSVT episodes (4–7 or ≥8 beats) were significantly associated with 2.3- to 2.8-fold increased annual SCD risk, especially when associated with the presence of myocardial ischemia irrespective of the presence of prior myocardial infarction (
      • Scirica B.M.
      • Braunwald E.
      • Belardinelli L.
      • Hedgepeth C.M.
      • Spinar J.
      • Wang W.
      • Morrow D.A.
      Relationship between nonsustained ventricular tachycardia after non-ST-elevation acute coronary syndrome and sudden cardiac death: Observations from the metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndrome-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) randomized controlled trial.
      ). While short-lasting NSVT episodes occurring within the first 48 hr after admission did not carry the same risk, similar episodes that occurred beyond 48 hr were associated with significant (2.9- to 3.7-fold) annual SCD risk. The failure to link an effective therapeutic intervention following these AECG findings has probably limited its utilization in clinical practice.
      In the late (>24 hr) postacute MI inpatient period, the detection of NSVT episodes has been associated with a higher rate of sustained VT and with subsequent increased mortality (
      • Cheema A.N.
      • Sheu K.
      • Parker M.
      • Kadish A.H.
      • Goldberger J.J.
      Nonsustained ventricular tachycardia in the setting of acute myocardial infarction: Tachycardia characteristics and their prognostic implications.
      ,
      • Pires L.A.
      • Lehmann M.H.
      • Buxton A.E.
      • Hafley G.E.
      • Lee K.L.
      Multicenter Unsustained Tachycardia Trial Investigators
      Differences in inducibility and prognosis of in-hospital versus out-of-hospital identified nonsustained ventricular tachycardia in patients with coronary artery disease: Clinical and trial design implications.
      ). Following discharge, NSVT has limited prognostic significance in post-MI patients. NSVT detection among MI survivors yielded low prognostic value for subsequent mortality and no prognostic value when only arrhythmic events were considered (
      • Hohnloser S.H.
      • Klingenheben T.
      • Zabel M.
      • Schopperl M.
      • Mauss O.
      Prevalence, characteristics and prognostic value during long-term follow-up of nonsustained ventricular tachycardia after myocardial infarction in the thrombolytic era.
      ). Although the presence of NSVT in 24-hr ECG recording was an independent predictor of adverse prognosis in the Autonomic Tone and Reflexes After Myocardial Infarction trial and raised interest in Holter monitoring for risk stratification (
      • La Rovere M.T.
      • Pinna G.D.
      • Hohnloser S.H.
      • Marcus F.I.
      • Mortara A.
      • Nohara R.
      ATRAMI Investigators
      Autonomic tone and reflexes after myocardial infarction. Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: Implications for clinical trials.
      ), in the current era in which post-MI patients are adequately reperfused and treated with beta-blockers, NSVT may not serve as an independent predictor of long-term mortality especially when other covariates such as LVEF are taken into account (
      • Bloch Thomsen P.E.
      • Jons C.
      • Raatikainen M.J.
      • Moerch Joergensen R.
      • Hartikainen J.
      • Virtanen V.
      Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) Study Group
      Long-term recording of cardiac arrhythmias with an implantable cardiac monitor in patients with reduced ejection fraction after acute myocardial infarction: The Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) study.
      ,
      • Hofsten D.E.
      • Wachtell K.
      • Lund B.
      • Molgaard H.
      • Egstrup K.
      Prevalence and prognostic implications of non-sustained ventricular tachycardia in ST-segment elevation myocardial infarction after revascularization with either fibrinolysis or primary angioplasty.
      ,
      • Katritsis D.G.
      • Siontis G.C.
      • Camm A.J.
      Prognostic significance of ambulatory ECG monitoring for ventricular arrhythmias.
      ). Therefore, AECG is currently not commonly used.
      After hospital discharge following MI, left ventricular scarring and remodeling may yield a suitable electrophysiological substrate for the genesis of both nonsustained and sustained ventricular arrhythmias. Although post-MI studies published in the early 1980s and 1990s identified frequent PVCs and NSVT as strong independent predictors of arrhythmia risk and SCD in MI survivors with left ventricular dysfunction (
      • Doval H.C.
      • Nul D.R.
      • Grancelli H.O.
      • Varini S.D.
      • Soifer S.
      • Corrado G.
      • Perrone S.V.
      Nonsustained ventricular tachycardia in severe heart failure. Independent marker of increased mortality due to sudden death. GESICA-GEMA Investigators.
      ), in the modern era, the independent predictive value of NSVT is not established (
      • Buxton A.E.
      • Lee K.L.
      • Hafley G.E.
      • Pires L.A.
      • Fisher J.D.
      • Gold M.R.
      MUSTT Investigators
      Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery disease: Lessons from the MUSTT study.
      ,
      • Katritsis D.G.
      • Siontis G.C.
      • Camm A.J.
      Prognostic significance of ambulatory ECG monitoring for ventricular arrhythmias.
      ,
      • Maggioni A.P.
      • Zuanetti G.
      • Franzosi M.G.
      • Rovelli F.
      • Santoro E.
      • Staszewsky L.
      • Tognoni G.
      Prevalence and prognostic significance of ventricular arrhythmias after acute myocardial infarction in the fibrinolytic era. GISSI-2 results.
      ,
      • Makikallio T.H.
      • Barthel P.
      • Schneider R.
      • Bauer A.
      • Tapanainen J.M.
      • Tulppo M.P.
      • Huikuri H.V.
      Prediction of sudden cardiac death after acute myocardial infarction: Role of Holter monitoring in the modern treatment era.
      ,
      • Singh S.N.
      • Fisher S.G.
      • Carson P.E.
      • Fletcher R.D.
      Prevalence and significance of nonsustained ventricular tachycardia in patients with premature ventricular contractions and heart failure treated with vasodilator therapy. Department of Veterans Affairs CHF STAT Investigators.
      ,
      • Teerlink J.R.
      • Jalaluddin M.
      • Anderson S.
      • Kukin M.L.
      • Eichhorn E.J.
      • Francis G.
      • Massie B.M.
      Ambulatory ventricular arrhythmias in patients with heart failure do not specifically predict an increased risk of sudden death. PROMISE (Prospective Randomized Milrinone Survival Evaluation) Investigators.
      ). This discrepancy could be explained by the extreme temporal variability of NSVT in different patient populations in association with the wide range in the timing of Holter recordings.
      On the other hand, NSVT was shown to be a significant predictor of SCD in post-MI patients with a relatively preserved ejection fraction (LVEF > 35%), independently of diabetes mellitus, age, and LVEF (
      • Makikallio T.H.
      • Barthel P.
      • Schneider R.
      • Bauer A.
      • Tapanainen J.M.
      • Tulppo M.P.
      • Huikuri H.V.
      Prediction of sudden cardiac death after acute myocardial infarction: Role of Holter monitoring in the modern treatment era.
      ). NSVT accompanied by inducibility of sustained VT during programmed ventricular stimulation was associated with an increased risk of SCD (
      • Buxton A.E.
      • Lee K.L.
      • Fisher J.D.
      • Josephson M.E.
      • Prystowsky E.N.
      • Hafley G.
      A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators.
      ,
      • Moss A.J.
      • Hall W.J.
      • Cannom D.S.
      • Daubert J.P.
      • Higgins S.L.
      • Klein H.
      • Heo M.
      Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators.
      ). Following the Multicenter Unsustained Tachycardia Trial (MUSTT) (
      • Buxton A.E.
      • Lee K.L.
      • Fisher J.D.
      • Josephson M.E.
      • Prystowsky E.N.
      • Hafley G.
      A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators.
      ), there is a role for AECG for NSVT detection in post-MI patients with LVEF 35%–40% as electrophysiologically guided ICD implantation improves survival (
      • Epstein A.E.
      • DiMarco J.P.
      • Ellenbogen K.A.
      • Estes 3rd, N.A.
      • Freedman R.A.
      • Gettes L.S.
      Heart Rhythm Society
      2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.
      ,
      • Priori S.G.
      • Blomström-Lundqvist C.
      • Mazzanti A.
      • Blom N.
      • Borggrefe M.
      • Camm J.
      • Van Veldhuisen D.J.
      2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC).
      ).
      In conclusion, in patients with prior MI treated with reperfusion and beta-blockers, NSVT is not an independent predictor of long-term mortality when other covariates such as LVEF are taken into account. Across studies of ischemic heart failure patients, the predictive value of irregular ventricular activity in ambulatory Holter recordings remains debatable. However, prolonged (>8 beats) and rapid (>120 beats per minute) episodes of NSVT may justify further exploration of the SCD risk by use of noninvasive or even invasive measures. The detection of any NSVT in patients with borderline EF (e.g., 35%–40%) might prompt further risk stratification and determination of need for ICD using EPS.

       5.2. Nonischemic dilated cardiomyopathy

      Nonischemic dilated cardiomyopathy (NIDCM) may be the consequence of a variety of causes, including virus-mediated and autoimmune disease, as well as toxic and metabolic, inherited, and tachycardia-induced conditions. Tachycardiomyopathy may result from atrial arrhythmias with rapid and/or irregular ventricular response or frequent ventricular ectopy. In such cases, AECG monitoring is useful to evaluate heart rate or frequency and complexity of ectopy in order to establish diagnosis and/or indications for invasive therapeutic treatment as ablation (
      • Baman T.S.
      • Lange D.C.
      • Ilg K.J.
      • Gupta S.K.
      • Liu T.Y.
      • Alguire C.
      • Bogun F.
      Relationship between burden of premature ventricular complexes and left ventricular function.
      ,
      • Pedersen C.T.
      • Kay G.N.
      • Kalman J.
      • Borggrefe M.
      • Della-Bella P.
      • Dickfeld T.
      • Savelieva I.
      EP-Europace, UK
      EHRA/HRS/APHRS expert consensus on ventricular arrhythmias.
      ).
      Patients with NIDCM die mostly from SCD or heart failure progression (
      • Okutucu S.
      • Oto A.
      Risk stratification in nonischemic dilated cardiomyopathy: Current perspectives.
      ). Theoretically, AECG monitoring may be considered as a tool in risk stratification of SCD by detection of NSVT episodes and evaluation of other Holter-based risk markers. However, in contradistinction to what is reported in patients with ischemic cardiomyopathy, the prognostic value of AECG in NIDCM is rather low and remains controversial (
      • Goldberger J.J.
      • Cain M.E.
      • Hohnloser S.H.
      • Kadish A.H.
      • Knight B.P.
      • Lauer M.S.
      Heart Rhythm Society
      American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society scientific statement on noninvasive risk stratification techniques for identifying patients at risk for sudden cardiac death. A scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention.
      ,
      • Goldberger J.J.
      • Subačius H.
      • Patel T.
      • Cunnane R.
      • Kadish A.H.
      Sudden cardiac death risk stratification in patients with nonischemic dilated cardiomyopathy.
      ,
      • Pedersen C.T.
      • Kay G.N.
      • Kalman J.
      • Borggrefe M.
      • Della-Bella P.
      • Dickfeld T.
      • Savelieva I.
      EP-Europace, UK
      EHRA/HRS/APHRS expert consensus on ventricular arrhythmias.
      ).
      The incidence of NSVT in patients with NIDCM varied from 33% to 79% (
      • Doval H.C.
      • Nul D.R.
      • Grancelli H.O.
      • Varini S.D.
      • Soifer S.
      • Corrado G.
      • Perrone S.V.
      Nonsustained ventricular tachycardia in severe heart failure. Independent marker of increased mortality due to sudden death. GESICA-GEMA Investigators.
      ,
      • Katritsis D.G.
      • Siontis G.C.
      • Camm A.J.
      Prognostic significance of ambulatory ECG monitoring for ventricular arrhythmias.
      ,
      • Okutucu S.
      • Oto A.
      Risk stratification in nonischemic dilated cardiomyopathy: Current perspectives.
      ).
      • Iacoviello M.
      • Forleo C.
      • Guida P.
      • Romito R.
      • Sorgente A.
      • Sorrentino S.
      • Pitzalis M.
      Ventricular repolarization dynamicity provides independent prognostic information toward major arrhythmic events in patients with idiopathic dilated cardiomyopathy.
      found that NSVT was associated with threefold higher risk of arrhythmic events during follow-up and that prognostic value of NSVT was enhanced by a combination with low LVEF and abnormal QT dynamics. In Marburg Cardiomyopathy study (
      • Grimm W.
      • Christ M.
      • Bach J.
      • Müller H.H.
      • Maisch B.
      Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: Results of the Marburg Cardiomyopathy Study.
      ), NSVT evaluated alone was not associated with an increased risk of arrhythmic events; however, when combined with low LVEF, the risk was eightfold higher. A meta-analysis by
      • de Sousa M.R.
      • Morillo C.A.
      • Rabelo F.T.
      • Nogueira Filho A.M.
      • Ribeiro A.L.
      Non-sustained ventricular tachycardia as a predictor of sudden cardiac death in patients with left ventricular dysfunction: A meta-analysis.
      showed that the presence of NSVT was a statistically significant predictor, independent of LVEF, of SCD in patients with NIDCM and depressed LVEF. A more recent meta-analysis by
      • Goldberger J.J.
      • Subačius H.
      • Patel T.
      • Cunnane R.
      • Kadish A.H.
      Sudden cardiac death risk stratification in patients with nonischemic dilated cardiomyopathy.
      based on 45 studies encompassing over 6,000 patients concluded that NSVT evaluated alone was a significant risk predictor (OR = 2.92, p < .001) of an arrhythmic endpoint defined as sudden or arrhythmic death, cardiac arrest, documented ICD therapy, and documented VT/VF. The negative predictive value of NSVT was as high as 90%; however, its positive predictive value was only 20%. This study summarized the prognostic role of multiple risk stratifiers and found that the best predictors of unfavorable outcome were TWA, left ventricular end diastolic diameter, EPS, signal averaged ECG, LVEF, QRS duration, and NSVT. None of the markers of autonomic dysfunction such as baroreflex sensitivity, HRV, and HRT was found to be statistically significant. Overall, the data regarding NSVT are weak and do not support routine use of noninvasive techniques in this population.

       5.3. Hypertrophic cardiomyopathy

      An unfavorable clinical course in HCM is related to an increased risk of SCD, progressive heart failure, and complications attributable to AF. HCM is the most common cause of SCD in young people, notably athletes (
      • Maron B.J.
      • Ommen S.R.
      • Semsarian C.
      • Spirito P.
      • Olivotto I.
      • Maron M.S.
      Hypertrophic cardiomyopathy: Present and future, with translation into contemporary cardiovascular medicine.
      ).
      Syncope and palpitations are among the most commonly reported complaints in patients with HCM (
      • Elliott P.M.
      • Anastasakis A.
      • Borger M.A.
      • Borggrefe M.
      • Cecchi F.
      • Charron P.
      • Watkins H.
      2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).
      ,
      • Finocchiaro G.
      • Pinamonti B.
      • Merlo M.
      • Brun F.
      • Barbati G.
      • Sinagra G.
      Prognostic role of clinical presentation in symptomatic patients with hypertrophic cardiomyopathy.
      ,
      • Gersh B.J.
      • Maron B.J.
      • Bonow R.O.
      • Dearani J.A.
      • Fifer M.A.
      • Link M.S.
      American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
      2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      ,
      • Monserrat L.
      • Elliott P.M.
      • Gimeno J.R.
      • Sharma S.
      • Penas-Lado M.
      • McKenna W.J.
      Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: An independent marker of sudden death risk in young patients.
      ). Syncopal episodes may be caused by conduction disturbances, paroxysmal atrial arrhythmias with rapid ventricular rate, LV outflow tract obstruction or neurally mediated events, and most ominously, potentially lethal ventricular arrhythmias. Up to 30% of HCM patients present with NSVT episodes on Holter monitoring (
      • Adabag A.S.
      • Casey S.A.
      • Kuskowski M.A.
      • Zenovich A.G.
      • Maron B.J.
      Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy.
      ,
      • Monserrat L.
      • Elliott P.M.
      • Gimeno J.R.
      • Sharma S.
      • Penas-Lado M.
      • McKenna W.J.
      Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: An independent marker of sudden death risk in young patients.
      ). The frequency is related to the degree of myocardial fibrosis (
      • Adabag A.S.
      • Maron B.J.
      • Appelbaum E.
      • Harrigan C.J.
      • Buros J.L.
      • Gibson C.M.
      • Maron M.S.
      Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance.
      ). As syncope is considered a risk factor for SCD in patients with HCM, careful workup including ECG, exercise test, and AECG should be performed. ACCF/AHA guidelines published in 2011 recommended 24-hr AECG monitoring, while 2014 ESC guidelines recommend longer 48-hr AECG monitoring in patients at their initial clinical assessment to detect atrial and ventricular arrhythmias (Class IB) (
      • Elliott P.M.
      • Anastasakis A.
      • Borger M.A.
      • Borggrefe M.
      • Cecchi F.
      • Charron P.
      • Watkins H.
      2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).
      ,
      • Gersh B.J.
      • Maron B.J.
      • Bonow R.O.
      • Dearani J.A.
      • Fifer M.A.
      • Link M.S.
      American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
      2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      ).
      Paroxysmal supraventricular arrhythmias (including AF) are observed in up to 38% of patients with HCM (
      • Elliott P.M.
      • Anastasakis A.
      • Borger M.A.
      • Borggrefe M.
      • Cecchi F.
      • Charron P.
      • Watkins H.
      2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).
      ,
      • Gersh B.J.
      • Maron B.J.
      • Bonow R.O.
      • Dearani J.A.
      • Fifer M.A.
      • Link M.S.
      American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
      2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      ) and are poorly tolerated, contributing to syncopal episodes or heart failure. According to ESC guidelines, HCM patients with left atrium diameter ≥45 mm, which is considered as a risk predictor for AF and stroke, should undergo 48 hr AECG every 6–12 months to detect AF even if asymptomatic (
      • Elliott P.M.
      • Anastasakis A.
      • Borger M.A.
      • Borggrefe M.
      • Cecchi F.
      • Charron P.
      • Watkins H.
      2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).
      ).
      Ambulatory ECG monitoring is an essential part of SCD risk stratification in patients with HCM, especially in younger subjects. Nevertheless, NSVT is characterized by high negative (95%) but low positive predictive values (
      • Adabag A.S.
      • Casey S.A.
      • Kuskowski M.A.
      • Zenovich A.G.
      • Maron B.J.
      Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy.
      ). Recently, published ESC guidelines recommend that the probability of sudden death at 5 years should be estimated based on the HCM Risk-SCD formula (
      • O'Mahony C.
      • Jichi F.
      • Pavlou M.
      • Monserrat L.
      • Anastasakis A.
      • Rapezzi C.
      Hypertrophic Cardiomyopathy Outcomes Investigators
      A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD).
      ). This “prognostic index” integrates detected NSVT with structural abnormalities and family history of SCD, unexplained syncope and age (class IB) (
      • Elliott P.M.
      • Anastasakis A.
      • Borger M.A.
      • Borggrefe M.
      • Cecchi F.
      • Charron P.
      • Watkins H.
      2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).
      ). 48-hr AECG monitoring to detect NSVT, defined as ≥3 PVCs at heart rate ≥120 bpm, together with clinical history and echocardiogram are considered as a first-line recommended assessment. Long NSVT episodes observed on AECG prior to an ICD implantation predicted appropriate ICD therapy during follow-up (
      • Francia P.
      • Santini D.
      • Musumeci B.
      • Semprini L.
      • Adduci C.
      • Pagannone E.
      • Autore C.
      Clinical impact of nonsustained ventricular tachycardia recorded by the implantable cardioverter-defibrillator in patients with hypertrophic cardiomyopathy.
      ). An index of NSVT severity (heart rate × length in beats/100 > 28) was associated with over fivefold higher risk of ICD intervention. If medical therapy is used to treat ventricular arrhythmias, AECG can be repeated.
      During follow-up, AECG monitoring should be repeated in the case of any symptoms suggestive of arrhythmia or routinely every 1–2 years to evaluate evidence of NSVT episodes (class IIa) or to detect asymptomatic AF episodes (class IIb) (
      • Gersh B.J.
      • Maron B.J.
      • Bonow R.O.
      • Dearani J.A.
      • Fifer M.A.
      • Link M.S.
      American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
      2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.
      ). ESC guidelines (
      • Elliott P.M.
      • Anastasakis A.
      • Borger M.A.
      • Borggrefe M.
      • Cecchi F.
      • Charron P.
      • Watkins H.
      2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).
      ) recommend longer recordings (48-hr) in all subjects and more frequent monitoring (every 6–12 months) in patients with a sinus rhythm and left atrium dimension ≥ 45 mm.

       5.4. Arrhythmogenic right ventricular dysplasia/Cardiomyopathy

      Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with a risk of SCD and/or progressive heart failure. Patients with ARVD/C may be asymptomatic or present with palpitations, dizziness, or syncope, potentially related to frequent ventricular ectopy or ventricular tachycardia episodes. Importantly, SCD may be the first manifestation of disease, especially in young athletes (
      • Corrado D.
      • Basso C.
      • Schiavon M.
      • Pelliccia A.
      • Thiene G.
      Pre-participation screening of young competitive athletes for prevention of sudden cardiac death.
      ).
      According to the 2010 revised Task Force criteria (
      • Marcus F.I.
      • McKenna W.J.
      • Sherrill D.
      • Basso C.
      • Bauce B.
      • Bluemke D.A.
      • Zareba W.
      Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: Proposed modification of the Task Force criteria.
      ), ARVD/C is diagnosed based on a multidimensional scoring system. Major arrhythmic criteria for diagnosis and risk stratification include the presence of nonsustained or sustained VT of LBBB morphology with superior axis. Minor criteria include nonsustained or sustained VT of RV outflow tract morphology, LBBB with inferior or unknown axis, and presence of >500 VPBs per 24 hr. Therefore, the initial evaluation of all patients suspected for ARVD/C should include 24-hr AECG monitoring. Extension of monitoring duration to capture arrhythmias may be considered. Significant day-to-day variability in PVC burden is noted in patients with ARVD/C, but
      • Camm C.F.
      • Tichnell C.
      • James C.A.
      • Murray B.
      • Porterfield F.
      • Te Riele A.S.
      • Calkins H.
      Premature ventricular contraction variability in arrhythmogenic right ventricular dysplasia/cardiomyopathy.
      reported that 24-hr AECG was sufficient to document the required Task Force criterion of over 500 PVCs in nearly 90% of cases, and extension of monitoring to 96 hr increased the number of correct classification to 95.5%.
      AECG has a role in patients already treated with an ICD. NSVT or PVC burden >1,000/24 hr may predict appropriate ICD discharge, the latter PVC burden associated with over threefold higher risk of ICD discharge (
      • Bhonsale A.
      • James C.A.
      • Tichnell C.
      • Murray B.
      • Gagarin D.
      • Philips B.
      • Calkins H.
      Incidence and predictors of implantable cardioverter-defibrillator therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing implantable cardioverter-defibrillator implantation for primary prevention.
      ). Identification of atrial arrhythmias is important as it may herald inappropriate ICD therapy, and is associated with a higher risk of heart transplantation and cardiac mortality in patients with ARVD/C (
      • Saguner A.M.
      • Ganahl S.
      • Kraus A.
      • Baldinger S.H.
      • Medeiros-Domingo A.
      • Saguner A.R.
      • Duru F.
      Clinical role of atrial arrhythmias in patients with arrhythmogenic right ventricular dysplasia.
      ).
      AECG monitoring should be performed during evaluation of all first-degree relatives of patients with ARVD (
      • Marcus F.I.
      • McKenna W.J.
      • Sherrill D.
      • Basso C.
      • Bauce B.
      • Bluemke D.A.
      • Zareba W.
      Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: Proposed modification of the Task Force criteria.
      ). Episodes of VT with right ventricular origin pattern or more than 200 PVCs/24 hr are suggestive of familial involvement. There is no consensus on the frequency of serial re-assessment of subjects suspected for ARVD/C, but yearly assessment is reasonable. Documented electrical abnormalities, such as abnormal ECG and/or Holter, may precede structural changes during a 4-year follow-up in a cohort of ARVD/C relatives (
      • te Riele A.S.
      • James C.A.
      • Bhonsale A.
      • Groeneweg J.A.
      • Camm C.F.
      • Murray B.
      • Calkins H.
      Malignant arrhythmogenic right ventricular dysplasia/cardiomyopathy with a normal 12-lead electrocardiogram: A rare but underrecognized clinical entity.
      ). Complex ventricular arrhythmia may be observed even when the surface ECG is normal (
      • te Riele A.S.
      • James C.A.
      • Rastegar N.
      • Bhonsale A.
      • Murray B.
      • Tichnell C.
      • Tandri H.
      Yield of serial evaluation in at-risk family members of patients with ARVD/C.
      ).

       5.5. Wolff–Parkinson–White syndrome

      Ambulatory ECG monitoring is potentially useful for evaluation of accessory pathway conduction properties in patients with Wolf–Parkinson–White syndrome. The risk of sudden death is related to rapid conduction across the pathway, particularly during AF, if the anterograde refractory period is short. During continuous ambulatory recordings, intermittent preexcitation or sudden loss of preexcitation with sinus rate acceleration is suggestive of “low risk,” for example, those that have a shortest pre-excited RR interval during AF >250 ms (
      • Skanes A.C.
      • Obeyesekere M.
      • Klein G.J.
      Electrophysiology testing and catheter ablation are helpful when evaluating asymptomatic patients with Wolff-Parkinson-White Pattern.
      ). AECG may also be helpful in identifying patients with WPW who have nonsustained runs of AF (
      • Santinelli V.
      • Radinovic A.
      • Manguso F.
      • Vicedomini G.
      • Gulletta S.
      • Paglino G.
      • Pappone C.
      The natural history of asymptomatic ventricular pre-excitation a long-term prospective follow-up study of 184 asymptomatic children.
      ).

       5.6. Inherited primary arrhythmic diseases

      Cardiac channelopathies constitute a heterogeneous group of inherited diseases such as long and short QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), early repolarization syndrome, and idiopathic VF, which are often caused by mutations in genes coding ion channels or regulatory proteins. They are characterized by lack of evident structural heart disease and high risk of sudden death due to ventricular tachyarrhythmias (
      • Priori S.G.
      • Wilde A.A.
      • Horie M.
      • Cho Y.
      • Behr E.R.
      • Berul C.
      • Tracy C.
      HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.
      ). Surface ECG is a prerequisite in diagnosing these conditions and in predicting their risk of dying suddenly. Phenotype ECG expression in chanelopathies is variable; therefore, AECG monitoring may be useful in assessment of transient electrical changes suggestive of a disease. However, in patients with inherited primary arrhythmia syndromes the most important role of AECG is attributed to detection of arrhythmias and risk stratification. It should be emphasized that HRS/EHRA/APHRS consensus on inherited primary arrhythmia syndromes (
      • Priori S.G.
      • Wilde A.A.
      • Horie M.
      • Cho Y.
      • Behr E.R.
      • Berul C.
      • Tracy C.
      HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.
      ) underlines the role of exhaustive evaluation of the origin of syncopal episodes in patients with chanelopathies. Syncope is considered a significant risk marker of SCD.

       5.6.1. Long QT syndrome

      The long QT syndrome (LQTS) is a hereditary channelopathy characterized by QT prolongation and propensity to syncope, cardiac arrest, or sudden death in association with torsade de pointes polymorphic VT that might deteriorate to ventricular fibrillation (
      • Zareba W.
      • Cygankiewicz I.
      Long QT syndrome and short QT syndrome.
      ). Recent guideline revisions suggest the diagnosis of LQTS is based on the presence of risk score ≥3 points and/or the presence of a prolonged QTc ≥480 ms interval on repeated ECGs or pathogenic mutation (
      • Priori S.G.
      • Blomström-Lundqvist C.
      • Mazzanti A.
      • Blom N.
      • Borggrefe M.
      • Camm J.
      • Van Veldhuisen D.J.
      2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC).
      ). The risk score increases in relation to significantly prolonged QTc, torsade de pointes arrhythmias, and syncope. QT measurements are based on surface ECG; however, AECG may reveal transient prolongation of QT interval and/or inappropriate QT adaptation to heart rate. Repolarization abnormalities are frequently related to periods with abrupt changes in heart rate. In case of progressively increasing or decreasing RR intervals, the QT interval shows a linear correlation with heart rate within physiological limits. However, in case of abrupt RR changes, the QT does not change adequately (
      • Merri M.
      • Moss A.J.
      • Benhorin J.
      • Locati E.H.
      • Alberti M.
      • Badilini F.
      Relationship between ventricular repolarization and cardiac cycle length during 24-hour electrocardiographic (Holter) recordings: Findings in normals and patients with Long QT Syndrome.
      ). It is also documented that RR changes in the form of “short–long” cycles may precede the onset of VT in patients with LQTS (
      • Locati E.H.
      • Maison-blanche P.
      • Dejode P.
      • Cauchemez B.
      • Coumel P.
      Spontaneous sequences of onset of torsade de pointes in patients with prolonged repolarization: Quantitative analysis of Holter recordings.
      ). AECG may be helpful in illustrating T-wave abnormalities, evaluation of R on T phenomenon, capture of T-wave alternans (an ominous finding), detection of nonsustained or sustained VT (especially torsade de pointes), in addition to identifying QT interval prolongation itself. While no doubts exist in subjects with QTc >500 ms, those with QTc <500 ms are frequently referred for exercise ECG testing and 24-hr Holter monitoring. The presence of QTc >500 ms at heart rates <100 beats per minute during exercise testing or Holter recordings may be indicative of LQTS, whereas values below 500 ms are within physiological range (
      • Molnar J.
      • Zhang F.
      • Weiss J.
      • Ehlert F.A.
      • Rosenthal J.E.
      Diurnal pattern of QTc interval: How long is prolonged? Possible relation to circadian triggers of cardiovascular events.
      ). Findings of inappropriate QT adaptation to heart rate or even transient QT prolongation would be clinically useful findings.
      Whether AECG monitoring is required for establishing diagnosis or help in therapeutic decisions such as ICD implantation or drug titration remains unresolved. The 12-lead ECG remains the gold standard for diagnosis, however. During follow-up, AECG can be used to assess efficacy of drug therapy and its potential adverse effects such as bradycardia. Regarding noninvasive ECG risk stratification, one may consider use of AECG for detection of increased QT variability/dispersion, which are considered markers of electrical instability and therefore related to higher risk of SCD.

       5.6.2. Short QT syndrome

      Short QT syndrome diagnosed in patients with QTc ≤340 ms is a cardiac channelopathy associated with consistently shortened QT interval and a predisposition to AF and SCD in patients with no structural heart disease (
      • Priori S.G.
      • Blomström-Lundqvist C.
      • Mazzanti A.
      • Blom N.
      • Borggrefe M.
      • Camm J.
      • Van Veldhuisen D.J.
      2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC).
      ). Clinical manifestation of short QT syndrome may vary from totally asymptomatic to SCD as the first symptom. In the largest database of short QT syndrome patients, history of syncope was found in 24% of subjects, and the initial symptom in 14%. Palpitations were experienced by 31% of patients and were attributed to documented AF or atrial flutter in the majority of cases (
      • Giustetto C.
      • Di Monte F.
      • Wolpert C.
      • Borggrefe M.
      • Schimpf R.
      • Sbragia P.
      • Gaita F.
      Short QT syndrome: Clinical findings and diagnostic-therapeutic implications.
      ). AECG in short QT syndrome is useful in identification of the cause of syncope and palpitations, particularly in detection of AF episodes, but has little role in diagnosis or guiding protective therapy.

       5.6.3. Brugada syndrome

      Brugada syndrome is a primary inherited electrical condition characterized by abnormal repolarization pattern in the right precordial ECG leads and predisposition to life-threatening ventricular arrhythmias. The ECG diagnosis depends on a pattern of J-point elevation of 2 mm with coved ST-segment elevation and inverted T wave in V1–V2, classified as the type 1 morphology (
      • Priori S.G.
      • Wilde A.A.
      • Horie M.
      • Cho Y.
      • Behr E.R.
      • Berul C.
      • Tracy C.
      HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.
      ,
      • Priori S.G.
      • Blomström-Lundqvist C.
      • Mazzanti A.
      • Blom N.
      • Borggrefe M.
      • Camm J.
      • Van Veldhuisen D.J.
      2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC).
      ), occurring spontaneously or after provocative testing. The ECG of patients with Brugada syndrome is highly variable and can fluctuate over time from type 1 to other types, or even normalize, and vice versa. Therefore, some have suggested the 12-lead AECG may be useful to reveal the transient Brugada ECG pattern in patients who are suspected of harboring Brugada syndrome. Recently,
      • Cerrato N.
      • Giustetto C.
      • Gribaudo E.
      • Richiardi E.
      • Barbonaglia L.
      • Scrocco C.
      • Gaita F.
      Prevalence of type 1 Brugada electrocardiographic pattern evaluated by twelve-lead twenty-four-hour holter monitoring.
      analyzed the prevalence of Brugada pattern type 1 in 12-lead 24-hr AECG recordings in a series of 251 patients from the Brugada Registry, including 30% of patients with spontaneous and 70% of drug-induced type 1 patterns. They found that “spontaneous” but intermittent ECG type 1 pattern could be detected in 20% of patients who were identified primarily from a “drug-induced” group. Transient Brugada pattern was observed predominantly in the afternoon hours, from 12 p.m. to 6 p.m. The authors suggested that 12-lead AECG monitoring may be used as a screening test to avoid drug challenge as a first-line diagnostic procedure. It has also been reported that a 12-lead Holter recording with V1–V2 electrodes displaced to the third intercostal space is more sensitive for detection of the ECG type 1 pattern than repeated 12-lead ECGs or Holters with conventionally placed leads (
      • Shimeno K.
      • Takagi M.
      • Maeda K.
      • Tatsumi H.
      • Doi A.
      • Yoshiyama M.
      Usefulness of multichannel Holter ECG recording in the third intercostal space for detecting type 1 Brugada ECG: Comparison with repeated 12-lead ECGs.
      ). Additionally, the AECG could be used to assess for other arrhythmias or ECG patterns that may be supportive of the diagnosis of BS in asymptomatic subjects such as AF, ST-T wave alternans, spontaneous LBBB, and PVCs.
      Lifesaving therapy, that is, ICD implantation, is available for Brugada syndrome, but because the diagnosis can prove elusive in symptomatic patients, extended AECG recording with and without special lead positions can be considered in patients with unexplained syncope when a suspicion of Brugada syndrome exists (e.g., based on family history, characteristic trigger [fever, specific medications]).

       5.6.4. Catecholaminergic polymorphic ventricular tachycardia

      Catecholaminergic polymorphic ventricular tachycardia is a rare but highly lethal inherited channelopathy characterized by exercise- or emotion-induced palpitations and/or syncope in early adolescence, in subjects with no structural heart disease. SCD risk in CPVT is related to adrenergic-induced bidirectional and polymorphic ventricular tachycardia. As resting surface ECG is not helpful for the diagnosis of suspected CPVT, further electrocardiographic evaluation and provocative testing should be pursued. These tests may include AECG monitoring to assess the presence of ventricular tachyarrhythmia during daily activities and emotional stress, and above all exercise stress test to evaluate relationship of ventricular arrhythmia with increased catecholamines. Ventricular ectopy usually appears at a heart rate of 110–130 bpm and tends to aggravate in number and complexity with an increasing heart rate. Adrenergically induced atrial arrhythmias are also common.
      Ambulatory ECG could be recommended as a measure of efficacy of drug treatment in patients with CPVT. Prior HRS/EHRA/APHRS statements recommended periodic AECG monitoring and exercise tests to determine the heart rate at which ventricular arrhythmia occurs and to evaluate the efficacy of arrhythmia suppression, although the presence of asymptomatic PVCs on Holter monitoring does not imply an unfavorable prognosis (
      • Hayashi M.
      • Denjoy I.
      • Extramiana F.
      • Maltret A.
      • Buisson N.R.
      • Lupoglazoff J.M.
      • Leenhardt A.
      Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia.
      ,
      • Priori S.G.
      • Wilde A.A.
      • Horie M.
      • Cho Y.
      • Behr E.R.
      • Berul C.
      • Tracy C.
      HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.
      ).

       5.6.5. Early repolarization syndrome

      Following the publication by
      • Haïssaguerre M.
      • Derval N.
      • Sacher F.
      • Jesel L.
      • Deisenhofer I.
      • de Roy L.
      • Clémenty J.
      Sudden cardiac arrest associated with early repolarization.
      , more attention is being paid to the early repolarization pattern that had for years been considered a benign ECG finding. Several studies have documented that J-point elevation in the inferior and/or lateral leads is frequently observed in patients with idiopathic VF. Nevertheless, such an ECG pattern may also be observed in up to 31% of the general population (
      • Macfarlane P.W.
      • Antzelevitch C.
      • Haissaguerre M.
      • Huikuri H.V.
      • Potse M.
      • Rosso R.
      • Yan G.X.
      The early repolarization pattern: A consensus paper.
      ,
      • Maury P.
      • Rollin A.
      Prevalence of early repolarisation/J wave patterns in the normal population.
      ,
      • Rosso R.
      • Kogan E.
      • Belhassen B.
      • Rozovski U.
      • Scheinman M.M.
      • Zeltser D.
      • Viskin S.
      J-point elevation in survivors of primary ventricular fibrillation and matched control subjects: Incidence and clinical significance.
      ). According to HRS/EHRA/APHRS consensus (
      • Priori S.G.
      • Wilde A.A.
      • Horie M.
      • Cho Y.
      • Behr E.R.
      • Berul C.
      • Tracy C.
      HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.
      ), AECG monitoring may contribute to documentation of early repolarization pattern especially during bradycardia in survivors of VF, although the vast majority is accomplished via standard ECG. Increase in J-point elevation amplitude preceding ventricular arrhythmias has been reported in ICD patients with electrical storm (
      • Nam G.B.
      • Ko K.H.
      • Kim J.
      • Park K.M.
      • Rhee K.S.
      • Choi K.J.
      • Antzelevitch C.
      Mode of onset of ventricular fibrillation in patients with early repolarization pattern vs Brugada syndrome.
      ).

       5.6.6. Idiopathic ventricular fibrillation

      Idiopathic ventricular fibrillation is a diagnosis by exclusion, defined as a resuscitated cardiac arrest, preferably with ECG documentation of VF, in subjects in whom cardiac, respiratory, metabolic, and toxicological etiologies have been excluded. Detailed analysis of cardiac arrest victims should include personal and family history, electrocardiology (surface ECG, signal averaged ECG and AECG), imaging techniques to rule out structural heart disease, provocative tests, electrophysiological study, ventricular biopsy, and genetic testing. Holter monitoring has been suggested in evaluation of first-degree relatives of idiopathic VF victims.

       5.7. Dialysis and chronic kidney disease

      The prevalence of chronic kidney disease is increasing, and it is now present in at least 15% of the adult population (
      • Coresh J.
      • Astor B.C.
      • Greene T.
      • Eknoyan G.
      • Levey A.S.
      Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.
      ). End-stage renal disease (ESRD) is characterized by extremely high mortality (20% per year), and up to 100 times higher rate of cardiovascular death, as compared to the general population (
      • Foley R.N.
      Clinical epidemiology of cardiac disease in dialysis patients: Left ventricular hypertrophy, ischemic heart disease, and cardiac failure.
      ). SCD is the most common cause of death in dialysis patients (
      • Cheung A.K.
      • Sarnak M.J.
      • Yan G.
      • Berkoben M.
      • Heyka R.
      • Kaufman A.
      • Levey A.S.
      Cardiac diseases in maintenance hemodialysis patients: Results of the HEMO Study.
      ). Fluctuations of electrolytes and fluid, a chronic inflammatory state, preserved systolic function, but left ventricular hypertrophy with diastolic dysfunction, silent myocardial ischemia, and repetitive myocardial injury from dialysis-induced myocardial stunning contribute to the substrate for SCD (
      • Bleyer A.J.
      • Hartman J.
      • Brannon P.C.
      • Reeves-Daniel A.
      • Satko S.G.
      • Russell G.
      Characteristics of sudden death in hemodialysis patients.
      ).
      However, data on the rate of asymptomatic cardiac arrhythmia in patients with ESRD between dialysis sessions are limited. Previous 24–48 Holter ECG studies reported conflicting findings regarding cardiac arrhythmia burden and ECG markers of SCD during and after dialysis.
      • Burton J.O.
      • Jefferies H.J.
      • Selby N.M.
      • McIntyre C.W.
      Hemodialysis-induced cardiac injury: Determinants and associated outcomes.
      showed that PVCs and VT were more common during hemodialysis than in the subsequent monitored period, and were associated with myocardial stunning. Silent myocardial ischemia was diagnosed on Holter in 22% of dialysis patients, and strongly associated with VT/VF during and after dialysis (
      • Mohi-ud-din K.
      • Bali H.K.
      • Banerjee S.
      • Sakhuja V.
      • Jha V.
      Silent myocardial ischemia and high-grade ventricular arrhythmias in patients on maintenance hemodialysis.
      ). Interestingly, silent myocardial ischemia did not correlate with significant coronary heart disease and was thought to be due to microvascular disease and coronary spasm. Dynamic ECG observations included a progressive increase in QRS voltage and heart rate, decrease in T-wave amplitude, and increased occurrence of arrhythmia during dialysis (
      • Rodriguez-Fernandez R.
      • Infante O.
      • Perez-Grovas H.
      • Hernandez E.
      • Ruiz-Palacios P.
      • Franco M.
      • Lerma C.
      Visual three-dimensional representation of beat-to-beat Electrocardiogram Traces During Hemodiafiltration.
      ).
      • Green D.
      • Batchvarov V.
      • Wijesekara C.
      • Kalra P.A.
      • Camm A.J.
      Dialysis-dependent changes in ventricular repolarization.
      reported that microvolt TWA increased during dialysis, but did not find association between TWA and cardiovascular outcomes during 2.6 years of follow-up. Recently, an association between higher serum hemoglobin level and frequency of PVCs during dialysis was shown, which might explain the detrimental effect of high hemoglobin level on hemodialysis patients (
      • Saygi S.
      • Asci G.
      • Dheir H.
      • Duman S.
      • Kayikcioglu M.
      • Yilmaz M.
      • Ok E.
      Ventricular arrhythmia in dialysis patients: A link with higher hemoglobin levels?.
      ).
      • Poulikakos D.
      • Banerjee D.
      • Malik M.
      T wave morphology changes during hemodialysis.
      showed that T-wave morphology undergoes uniform rate-dependent changes during the dialysis procedure, whereas QRS-T angle changes differ from person to person, and correlated with the level of parathyroid hormone.
      Recently,
      • Buiten M.S.
      • de Bie M.K.
      • Rotmans J.I.
      • Gabreels B.A.
      • van Dorp W.
      • Wolterbeek R.
      • van Erven L.
      The dialysis procedure as a trigger for atrial fibrillation: New insights in the development of atrial fibrillation in dialysis patients.
      showed that the dialysis procedure itself is associated with the development of AF. Patients receiving peritoneal dialysis showed significantly fewer episodes of AF. AF onset was more frequent on the days of the hemodialysis procedure, and during the dialysis procedure itself. Therefore, AECG monitoring during dialysis could help with the earlier diagnosis of AF in asymptomatic patients, which may prompt appropriate AF management including anticoagulant therapy.

       5.8. Neurological and muscular diseases

      Perturbation of the balance of the autonomic nervous system can be studied by AECG, particularly through the analysis of HRV. Reduced HRV is generally associated with an elevated sympathetic tone or reduced parasympathetic activity. Activation of the autonomic nervous system can contribute to the genesis of a variety of arrhythmias, including both brady- and tachyarrhythmias. A strong link between epilepsy and cardiac arrhythmias has been described. Recordings during seizures report that sinus tachycardia just prior to the seizure is common, with both atrial and ventricular ectopy also observed. However, life-threatening arrhythmias and sudden death in epileptic patients are uncommon, with a rate of approximately two in a thousand. It is possible that the same cellular mechanisms triggering cardiac arrhythmias may be responsible for cerebral epilepsy.
      Myotonic dystrophy is a progressive genetic condition that primarily affects skeletal muscle but has important cardiac complications (
      • Groh W.J.
      • Groh M.R.
      • Saha C.
      • Kincaid J.C.
      • Simmons Z.
      • Ciafaloni E.
      • Pascuzzi R.M.
      Electrocardiographic abnormalities and sudden death in myotonic dystrophy type I.
      ). A variety of bradyarrhythmias have been observed, including sinus node dysfunction, bundle branch block, and the entire spectrum of AV blocks. Patients may also experience AF and sustained VT. Sudden death is reportedly due to asystole and ventricular fibrillation, and some patients may benefit from pacemaker or ICD. AECG may be used to detect arrhythmias to guide device and medical management, but there is little published data to guide its specific use in this clinical context.

       5.9. Sleep apnea

      Sleep apnea syndrome is a common breathing disorder that affects 2%–4% of the population, with men being affected almost twice as often as women (
      • Baranchuk A.
      • Simpson C.S.
      • Redfearn D.P.
      • Fitzpatrick M.
      It's time to wake up!: Sleep apnea and cardiac arrhythmias.
      ). The condition has well-defined associations with increased cardiovascular morbidity and mortality, arrhythmia, daytime hypersomnolence, motor vehicle accidents, and neurocognitive dysfunction, yet it is grossly underdiagnosed (
      • Hersi A.S.
      Obstructive sleep apnea and cardiac arrhythmias.
      ).
      Recent studies have shown that cardiac arrhythmias and conduction disorders are common in patients with sleep apnea (
      • Hersi A.S.
      Obstructive sleep apnea and cardiac arrhythmias.
      ,
      • Todd K.
      • McIntyre W.F.
      • Baranchuk A.
      Obstructive sleep apnea and atrial fibrillation.
      ). The mechanisms of this association include autonomic imbalance, systemic and pulmonary hypertension, intermittent hypoxia, and inflammation. All these conditions facilitate structural and electrical remodeling, which is considered to be the electrical substrate for a variety of arrhythmias (
      • Baranchuk A.
      Sleep apnea, cardiac arrhythmias and conduction disorders.
      ).
      The cornerstone for the diagnosis of sleep apnea is polysomnography, during which a variety of cardiac arrhythmias (AV block, sinus pauses, NSVT, and paroxysmal AF) can be detected (
      • Monahan K.
      • Storfer-Isser A.
      • Mehra R.
      • Shahar E.
      • Mittleman M.
      • Rottman J.
      • Redline S.
      Triggering of nocturnal arrhythmias by sleep-disordered breathing events.
      ). Because polysomnography is not universally available and can be logistically cumbersome, screening larger populations at risk would be advantaged by simpler and less expensive diagnostic tests. It has been proposed that the Holter monitor may fill this role. Additional information beyond what is typical for Holter recordings include a description from the patient about hours of sleep. Some commercial systems include apnea analysis algorithms that use: (1) breathing-related changes in sinus rhythm, that is, sinus arrhythmia, modulated by the ANS; and/or (2) changes in R-wave amplitude modified by respiratory movement of the chest wall resulting in subtle shift of the distance between ECG electrodes. More validation of these techniques is needed.

       5.10. Athletes and precompetition screening

      Arrhythmia monitoring of the athlete is, in some ways, distinct from utilization of monitoring in other circumstances. For the athlete, symptoms suspicious of an arrhythmia, rarely, can be a premonitory sign of SCD and may indicate an otherwise potentially serious but treatable condition or arrhythmia. On the other hand, undue restriction for suspicious but benign symptoms may be unwarranted.
      A stepwise approach to evaluating the athlete should be considered. First, it is important to understand historical features of the symptoms involved and if they are related to specific competitive or physical activities. Second, it is important to rule out important cardiovascular disease that may be present concomitantly or be the initiator of the arrhythmia.
      An ECG and other noninvasive tests are performed to determine the presence of any underlying structural process that could be involved and require restriction from athletics. On the ECG, there may be obvious features that point to a specific arrhythmogenic substrate. However, for many competitive athletes, the sport itself is required to initiate the symptom and potentially the arrhythmia. Furthermore, any symptom and/or arrhythmia may not necessarily be reproducible. Thus, the AECG is one of several subsequent steps in evaluating the patient depending on the sport, the athlete, the circumstances of the symptoms, and the presence of comorbidities as well as family history.
      Ambulatory ECG monitoring for the athlete is specifically useful when (1) the athlete is not already restricted due to a diagnosed cardiovascular condition; (2) there is no other way to secure a diagnosis or cause for the symptoms with any certainty; and (3) participation in athletics causes the symptoms and may facilitate the arrhythmia diagnosis. ECG monitoring can be used to secure an initial diagnosis or as a surveillance tool to ascertain that an arrhythmia is eliminated by therapy. AECG should be considered to correlate symptoms (e.g., syncope, palpitations) with arrhythmia. In addition, it may be helpful in asymptomatic patients when the initial screening ECG suggests high-density or complex ventricular ectopy to quantify the ventricular arrhythmia burden (
      • Zipes D.P.
      • Link M.S.
      • Ackerman M.J.
      • Kovacs R.J.
      • Myerburg R.J.
      • Estes 3rd, N.A.
      The American College of Cardiology
      Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 9: Arrhythmias and conduction defects: A Scientific Statement From the American Heart Association and American College of Cardiology.
      ). Very frequent ventricular ectopy may suggest the presence of underlying heart disease (
      • Biffi A.
      • Pelliccia A.
      • Verdile L.
      • Fernando F.
      • Spataro A.
      • Caselli S.
      • Maron B.J.
      Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes.
      ). In addition, some known heart conditions (e.g., congenital aortic stenosis, low-risk cardiomyopathy) and baseline ECG abnormalities (e.g., AV block, bundle branch block) may be further worked up with AECG (
      • Pelliccia A.
      • Fagard R.
      • Bjørnstad H.H.
      • Anastassakis A.
      • Arbustini E.
      • Assanelli D.
      Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology
      Recommendations for competitive sports participation in athletes with cardiovascular disease: A consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology.
      ).
      The type of monitoring depends on symptom frequency, severity, duration, and type of circumstances surrounding the symptoms. In addition, the type of monitoring depends on the type of athletic participation and the arrhythmia and symptom being assessed. There is no one best monitoring technique, and individualized decisions are needed.
      Rhythm disturbances, by themselves, do not necessarily elicit symptoms, and some rhythm disturbances can occur with or without symptoms. On the other hand, patients may have multiple rhythm disturbances and recording an asymptomatic rhythm disturbance does not necessarily imply high risk.

      6. Section 4: Holter-Based Markers of Autonomic Nervous Tone and Repolarization

      Candidate selection for ICD therapy could be improved. Implantation according to current guidelines results in appropriate therapy in only about 20% of patients with ICDs. In addition, current indications neglect the vast majority of patients vulnerable to SCD who have relatively preserved LVEF. Accounting for the multifactorial pathogenesis of SCD including structural substrate, autonomic dysfunction, and repolarization abnormalities may improve specificity.

       6.1. Heart rate variability

      Heart rate variability is one of the oldest Holter-based risk stratification tools as well as the most extensively used. It detects autonomic nervous system tone based on beat-to-beat RR intervals. Studies have demonstrated the correlation of depressed HRV with risk of mortality including cardiovascular death but not with SCD (
      Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology
      Heart rate variability. Standards of measurement, physiological interpretation and clinical use.
      ,
      • Sassi R.
      • Cerutti S.
      • Lombardi F.
      • Malik M.
      • Huikuri H.V.
      • Peng C.K.
      • Yamamoto Y.
      Advances in heart rate variability signal analysis: Joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society.
      ,
      • Wellens H.J.
      • Schwartz P.J.
      • Lindemans F.W.
      • Buxton A.E.
      • Goldberger J.J.
      • Hohnloser S.H.
      • Wilde A.A.
      Risk stratification for sudden cardiac death: Current status and challenges for the future.
      ).
      Measurement of HRV is performed in the frequency and time domains as well as by nonlinear techniques. Frequency-domain parameters require data stationarity and typically employ short-term recordings under controlled conditions but can also be performed over 24 hr from 5-min segments averaged over the entire period. Time-domain parameters measure changes in NN intervals often based on long-term recordings, typically 18 hr encompassing morning and night. Standard deviation of all NN intervals (SDNN) is the oldest, the simplest, and the most frequently used time-domain HRV parameter. Nonlinear HRV analysis is believed to be less dependent on preprocessing and to express better the complexity of RR changes (
      • Perkiomaki J.S.
      • Makikallio T.H.
      • Huikuri H.V.
      Nonlinear analysis of heart rate variability: Fractal and complexity measures of heart rate behaviour.
      ). The methodology of HRV measurement is summarized in a report of the Task Force of ESC/NASPE and in recently published joint position statement by e-Cardiology Working Group of ESC/EHRA/APHRS (
      Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology
      Heart rate variability. Standards of measurement, physiological interpretation and clinical use.
      ,
      • Sassi R.
      • Cerutti S.
      • Lombardi F.
      • Malik M.
      • Huikuri H.V.
      • Peng C.K.
      • Yamamoto Y.
      Advances in heart rate variability signal analysis: Joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society.
      ).
      Decreased HRV values have been consistently reported in post-MI infarction and heart failure patients (
      • Bigger Jr., J.T.
      • Fleiss J.L.
      • Steinman R.C.
      • Rolnitzky L.M.
      • Kleiger R.E.
      • Rottman J.N.
      Frequency domain measures of heart period variability and mortality after myocardial infarction.
      ,
      • Kleiger R.E.
      • Miller J.P.
      • Bigger J.T.
      • Moss A.J.
      The Multicenter Post-Infarction Research Group
      Decreased heart rate variability and its association with increased mortality after acute myocardial infarction.
      ,
      • La Rovere M.T.
      • Pinna G.D.
      • Maestri R.
      • Mortara A.
      • Capomolla S.
      • Febo O.
      • Cobelli F.
      Short-term heart rate variability strongly predicts sudden death in chronic heart failure.
      ,
      • La Rovere M.T.
      • Pinna G.D.
      • Maestri R.
      • Barlera S.
      • Bernardinangeli M.
      • Veniani M.
      GISSI-HF Investigators
      Autonomic markers and cardiovascular and arrhythmic events in heart failure patients: Still a place in prognostication? Data from the GISSI-HF trial.
      ,
      • Makikallio T.H.
      • Barthel P.
      • Schneider R.
      • Bauer A.
      • Tapanainen J.M.
      • Tulppo M.P.
      • Huikuri H.V.
      Prediction of sudden cardiac death after acute myocardial infarction: Role of Holter monitoring in the modern treatment era.
      ). The clinical relevance of abnormal HRV, namely, increased sympathetic tone and/or decreased vagal activity, as a predictor of overall mortality was appreciated as early as in the 1980s, when
      • Kleiger R.E.
      • Miller J.P.
      • Bigger J.T.
      • Moss A.J.
      The Multicenter Post-Infarction Research Group
      Decreased heart rate variability and its association with increased mortality after acute myocardial infarction.
      first reported that SDNN <50 ms was associated with fivefold higher mortality in postmyocardial infarction patients compared to those with SDNN > 50 ms. Multiple studies have consistently confirmed the prognostic value of HRV in predicting overall mortality and heart failure progression (
      • La Rovere M.T.
      • Pinna G.D.
      • Maestri R.
      • Mortara A.
      • Capomolla S.
      • Febo O.
      • Cobelli F.
      Short-term heart rate variability strongly predicts sudden death in chronic heart failure.
      ,
      • La Rovere M.T.
      • Pinna G.D.
      • Maestri R.
      • Barlera S.
      • Bernardinangeli M.
      • Veniani M.
      GISSI-HF Investigators
      Autonomic markers and cardiovascular and arrhythmic events in heart failure patients: Still a place in prognostication? Data from the GISSI-HF trial.
      ). Recent studies, performed in modern postmyocardial infarction cohorts treated with beta-blockers and early reperfusion, have reported conflicting results. The REFINE study failed to demonstrate the usefulness of decreased SDNN in predicting cardiac death or resuscitated cardiac arrest in 322 acute postmyocardial infarction patients with LVEF <50% (
      • Exner D.V.
      • Kavanagh K.M.
      • Slawnych M.P.
      • Mitchell L.B.
      • Ramadan D.
      • Aggarwal S.G.
      • Duff H.J.
      REFINE Investigators
      Noninvasive risk assessment early after a myocardial infarction the REFINE study.
      ). By contrast, the CARISMA trial investigators reported that in 312 patients evaluated at 6 weeks after an acute myocardial infarction, SDNN, very low frequency (VLF), high frequency (HF), and fractal scaling component independently predicted all-cause mortality and arrhythmic events documented by an ILR (
      • Huikuri H.V.
      • Raatikainen M.J.
      • Moerch-Joergensen R.
      • Hartikainen J.
      • Virtanen V.
      • Boland J.
      Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction Study Group
      Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction.
      ). In heart failure patients, decreased HRV has been documented as a potent marker of heart failure progression and identified patients in need of heart transplantation or with elevated risk for death due to pump failure. The GISSI Holter substudy in a contemporary population of heart failure patients showed that SDNN, VLF, LF, and detrended fluctuation analysis were independent risk predictors for cardiovascular death, while VLF and LF were associated with sudden death or appropriate ICD discharge (
      • La Rovere M.T.
      • Pinna G.D.
      • Maestri R.
      • Barlera S.
      • Bernardinangeli M.
      • Veniani M.
      GISSI-HF Investigators
      Autonomic markers and cardiovascular and arrhythmic events in heart failure patients: Still a place in prognostication? Data from the GISSI-HF trial.
      ).
      Despite data linking decreased HRV with increased mortality, randomized trials in patients stratified for ICD implantation based on this parameter failed to demonstrate the usefulness of HRV in predicting benefit from ICD therapy (
      • Hohnloser S.H.
      • Kuck K.H.
      • Dorian P.
      • Roberts R.S.
      • Hampton J.R.
      • Hatala R.
      DINAMIT Investigators
      Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction.
      ,
      • Steinbeck G.
      • Andresen D.
      • Seidl K.
      • Brachmann J.
      • Hoffmann E.
      • Wojciechowski D.
      • Senges J.
      IRIS Investigators
      Defibrillator implantation early after myocardial infarction.
      ). Patients with impaired HRV at enrollment were more likely to die from heart failure progression than from arrhythmic causes. In fact, HRV algorithms are currently implemented in cardiac resynchronization therapy (CRT) devices to identify heart failure exacerbation (
      • Landolina M.
      • Gasparini M.
      • Lunati M.
      • Santini M.
      • Rordorf R.
      • Vincenti A.
      InSync/InSync ICD Italian Registry Investigators
      Heart rate variability monitored by the implanted device predicts response to CRT and long-term clinical outcome in patients with advanced heart failure.
      ). Additionally, the DEFINITE trial showed that preserved HRV, defined as SDNN >100 ms, identified patients without sudden death or ICD shocks during a 3-year follow-up (
      • Rashba E.J.
      • Estes N.A.
      • Wang P.
      • Schaechter A.
      • Howard A.
      • Zareba W.
      • Kadish A.
      Preserved heart rate variability identifies low-risk patients with nonischemic dilated cardiomyopathy: Results from the DEFINITE trial.
      ). Most commercial Holter systems are equipped with software for automated analysis of time- and frequency-domain HRV measures.

       6.2. Heart rate turbulence

      Heart rate turbulence analyzes the baroreceptor-mediated response of the sinus node to premature ventricular beats composed of an early acceleration and subsequent deceleration and is an indicator of baroreceptor sensitivity (
      • Schmidt G.
      • Malik M.
      • Barthel P.
      • Schneider R.
      • Ulm K.
      • Rolnitzky L.
      • Schomig A.
      Heart rate turbulence after ventricular premature beats as a predictor of mortality after myocardial infarction.
      ,
      • Bauer A.
      • Malik M.
      • Schmidt G.
      • Barthel P.
      • Bonnemeier H.
      • Cygankiewicz I.
      • Zareba W.
      Heart rate turbulence: Standards of measurement, physiological interpretation, and clinical use: International Society for Holter and Noninvasive Electrophysiology Consensus.
      ). Changes in RR intervals following PVCs are subtle and require dedicated software for calculation. Only Holter recordings with ≥5 PVCs are considered reliable for HRT calculation. Detailed HRT methodology is summarized in the ISHNE-sponsored consensus document (
      • Bauer A.
      • Malik M.
      • Schmidt G.
      • Barthel P.
      • Bonnemeier H.
      • Cygankiewicz I.
      • Zareba W.
      Heart rate turbulence: Standards of measurement, physiological interpretation, and clinical use: International Society for Holter and Noninvasive Electrophysiology Consensus.
      ).
      Abnormal HRT parameters have been documented in various subsets of patients following myocardial infarction, or patients with heart failure or other cardiac and noncardiac diseases such as diabetes, obstructive sleep apnea, or connective tissue diseases (
      • Barthel P.
      • Schneider R.
      • Bauer A.
      • Ulm K.
      • Schmitt C.
      • Schömig A.
      • Schmidt G.
      Risk stratification after acute myocardial infarction by heart rate turbulence.
      ,
      • Bauer A.
      • Malik M.
      • Schmidt G.
      • Barthel P.
      • Bonnemeier H.
      • Cygankiewicz I.
      • Zareba W.
      Heart rate turbulence: Standards of measurement, physiological interpretation, and clinical use: International Society for Holter and Noninvasive Electrophysiology Consensus.
      ,
      • Cygankiewicz I.
      • Zareba W.
      • Vazquez R.
      • Almendral J.
      • Bayes-Genis A.
      • Fiol M.
      MUSIC Investigators
      Prognostic value of QT/RR slope in predicting mortality in patients with congestive heart failure.
      ,
      • Cygankiewicz I.
      • Zareba W.
      • Vazquez R.
      • Vallverdu M.
      • Gonzalez-Juanatey J.R.
      • Valdes M.
      Muerte Subita en Insuficiencia Cardiaca Investigators
      Heart rate turbulence predicts all-cause mortality and sudden death in congestive heart failure patients.
      ,
      • Exner D.V.
      • Kavanagh K.M.
      • Slawnych M.P.
      • Mitchell L.B.
      • Ramadan D.
      • Aggarwal S.G.
      • Duff H.J.
      REFINE Investigators
      Noninvasive risk assessment early after a myocardial infarction the REFINE study.
      ,
      • Huikuri H.V.
      • Raatikainen M.J.
      • Moerch-Joergensen R.
      • Hartikainen J.
      • Virtanen V.
      • Boland J.
      Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction Study Group
      Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction.
      ,
      • Schmidt G.
      • Malik M.
      • Barthel P.
      • Schneider R.
      • Ulm K.
      • Rolnitzky L.
      • Schomig A.
      Heart rate turbulence after ventricular premature beats as a predictor of mortality after myocardial infarction.
      ). Clinical and ECG covariates such as age, LVEF, NYHA class, heart rate, number of PVCs, pharmacotherapy, and invasive therapeutic strategies influence HRT results (
      • Bauer A.
      • Malik M.
      • Schmidt G.
      • Barthel P.
      • Bonnemeier H.
      • Cygankiewicz I.
      • Zareba W.
      Heart rate turbulence: Standards of measurement, physiological interpretation, and clinical use: International Society for Holter and Noninvasive Electrophysiology Consensus.
      ,
      • Cygankiewicz I.
      Heart rate turbulence.