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ECG Monitoring in Syncope Martin H. Ruwald⁎, Wojciech Zareba Cardiology Division, Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, NY, USA
A R T I C LE I N F O
AB ST R A C T
Keywords:
Electrocardiographic (ECG) monitoring is a well-established procedure in the work-up of
Syncope
patients with syncope or for diagnosing arrhythmias. The investigation of syncope remains,
ECG monitoring
however, challenging and physicians have an increasing armamentarium of diagnostic
Diagnosis
tools available and with advances in technology the role of these tools has to be
Risk stratification
continuously evaluated. The gold standard for the diagnosis of syncope is a symptom– ECG correlation, and while many studies have investigated the use and indications of both short-term and long-term monitoring; there is still some uncertainty in their clinical utility and practical approach. The use of ECG monitoring and other diagnostic tools is often subject to a “shot-gun approach” rather than a strict guideline algorithm. A systematic approach and selection of ECG monitoring tools helps permit an effective usage of the limited health care resources available for the management of unexplained syncope. In this review we aim to focus and clarify the role of short-term (Holter and external loop recorders) and long-term (implantable loop recorders) ECG monitoring in the diagnosis and management of patients with unexplained syncope. © 2013 Elsevier Inc. All rights reserved.
Syncope and recurrent syncope are frequent causes of hospitalization and they remain common problems in the general population.1,2 The etiological diagnosis and assessment of syncope is challenging for the physician due to the unpredictability of the symptom, the unknown rate of recurrence and the short- and long-term risks associated with the variable causes of the syncope. The prognosis in syncope varies markedly with both underlying comorbidities and the etiological causality of the syncopal event. 2-8 The initial investigations (history, physical examination, ECG and orthostatic blood pressure measurements) can provide the diagnosis in up to 50% of the cases. 9,10 When the diagnosis is made no further testing is usually needed and appropriate therapy can be applied. For the remaining cases where the diagnosis is uncertain, the risk assessment and
suspected etiology of the syncope determine the further diagnostic approach (Fig 1). The criteria to determine whether the patient is at short- or long-term high-risk or low-risk is covered extensively in the European Society of Cardiology guidelines from 200911 and has been evaluated by several studies from emergency departments and are referenced here in Table 1.11 If arrhythmogenic syncope is suspected in high-risk patients, the patient should be evaluated with inpatient telemetry for 24–72 hours. If arrhythmogenic syncope is suspected and the patient is determined to be at low- or intermediate-risk, short- or longterm ECG monitoring can be applied depending on expected rate of recurrence. When is arrhythmogenic syncope suspected? The clinical features suggesting arrhythmogenic syncope includes synco-
Statement of Conflict of Interest: see page 209. ⁎ Address reprint requests to Martin H. Ruwald, MD, PhD, Heart Research Follow-up Program, University of Rochester Medical Center, 265 Crittenden Boulevard, Rochester, NY 14642. E-mail address: [email protected] (M.H. Ruwald). 0033-0620/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pcad.2013.08.007
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Abbreviations and Acronyms
pe while supine or on exertion, palpitations ECG = electrocardiogram prior to syncope, ECG ELR = external loop recorder abnormalities at the initial evaluation, the ICD = implantable cardioverter/ presence of structural defibrillator heart disease and a ILR = implantable loop recorder family history of sudden death (Tables 2 MCOT = mobile cardiac outpaand 3). This review tient telemegtry focuses on the use and indications of ECG monitoring in the evaluation of a patient with syncope based on the current evidence.
Electrocardiographic monitoring ECG monitoring is the method of choice for establishing symptom–ECG correlation and is considered the gold standard for diagnosing arrhythmogenic syncope. The diagnostic approach therefore involves varying durations of monitoring intervals in the hope of obtaining this important correlation. In this context it is important to remember that cardioinhibitory reflex (neutrally mediated) syncope also presents itself as an arrhythmia (most often asystole) when monitored by ECG.12,13 Abnormal ECGs are also well correlated with brady- or/and tachyarrhythmic causes of syncope when these patients are evaluated by an electrophysiologic
study.14 Thus mechanism and etiology of syncope do not always correlate. Similar mechanisms of syncope are present in various etiologies, and all etiologic manifestations can cause syncope by different mechanisms, that is, bradycardia or asystole in both vasovagal and cardiac etiology. This fact has led to studies investigating efficacy of treatment by mechanism. In the Eastbourne Syncope Assessment Study (EaSyAS),15 patients with an implantable loop recorder (ILR) leading to an ECG-directed specific treatment had a significant reduction of syncope recurrences. On the other hand the syncopal recurrence rate did not differ among subgroups in the Evaluation of Guidelines in SYncope Study 2 (EGSYS 2) where treatment was based on the established syncopal etiology.16 Since there is a therapeutic consequence in establishing the causal mechanism rather than the causal pathophysiological etiology (i.e. permanent cardiac pacing when documented asystolic pauses are present in vasovagal (neutrally mediated) syncope),this may be the most appropriate approach when evaluating syncope by means of electrocardiographic monitoring systems.17 As many as 50% of all syncopal events in patients with no apparent heart disease present as arrhythmias when the patients have been subject to investigations with implantable loop recorder (ILR).12,18 If the patient experiences a recurrence while monitored and no symptom–ECG correlation was evident, this allows for elimination of an arrhythmogenic mechanism. However during the period of monitoring, many asymptomatic arrhythmias are also recorded and how should those be dealt with? Finally there is the potential for serious
Fig 1 – The use of ECG monitoring in the work-up of syncope.
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Table 1 – Risk markers in unselected patients with syncope. Scheme
Clinical Markers
Short-term risk San Francisco Syncope Abnormal ECG Rule Low blood pressure Heart failure Shortness of breath Hematocrit less than 30% STePS Abnormal ECG Trauma at syncope No warning of syncope Male sex ROSE rule Abnormal ECG Elevated BNP levels Chest pain Fecal blood Long-term risk OESIL score Abnormal ECG Age above 65 years History of cardiovascular disease No warning of syncope Martin et al. Abnormal ECG Heart failure Shortness of breath Age above 45 years Ventricular arrhythmia EGSYS score Abnormal ECG Palpitations prior to syncope History of cardiovascular disease Syncope during exertion or while supine
injury or death during this “passive” monitoring period so the selection of patients has to be precise so as to avoid fatal outcomes. These are concerning issues in the current management of syncope patients during the period of ECG monitoring.
Selection of patients for telemetry during inpatient hospitalization For short-term high-risk patients suspected of arrhythmiogenic syncope (essentially all high-risk patients at risk of sudden cardiac death or major cardiac events) current guidelines recommend prompt hospitalization.11 Essentially the factors associated with short-term high risks are very similar to the factors associated with high probability of arrhythmogenic syncope and factors associated with short-
Table 2 – Baseline clinical features suggesting arrhythmogenic syncope. Syncope during exercise or in a supine position Palpitations prior to or at the time of syncope A family history of sudden death A history of cardiac disease (heart failure, low ejection fraction or previous myocardial infarction) Adapted from the ESC guidelines.11
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term adverse outcome in the risk stratification studies from emergency department (a combination of Tables 1 and 2). A necessity for prompt hospitalization and telemetry could therefore also include patients where the initial ECG shows features suggesting a high-risk despite a history and/or physical examination that is negative or seems to be low risk. Such conditions include but are not limited to the Brugada syndrome, short- and long-QT syndrome, arrhythmogenic right ventricular dysplasia, high-degree atrioventricular block and ventricular tachycardia.11 In the randomized Syncope Evaluation in the Emergency Department Study (SEEDS)19 a novel syncope unit significantly improved the diagnostic yield in the emergency department and reduced hospital admissions without affecting recurrent syncope or all-cause mortality for patients with intermediate risk. These findings provided benchmark results for optimizing and improving patient care and effectively utilizing healthcare resources. Syncope units and specialized care pathways for syncope patients have unfortunately not yet been widely implemented.20 Telemetry is usually performed from 24 to 72 hours, but currently no data support a specific duration for telemetry. Telemetry and admission are warranted due to high shortterm risk of sudden cardiac death, or ventricular arrhythmias even though the diagnostic yield may be rather low (16%) even in these pre-selected patients.21 Basically, however, no studies have investigated the value of in-hospital ECG monitoring of syncope in high-risk patients if (1) telemetry proves unhelpful in the diagnostic progress, (2) other inhospital diagnostic approaches (i.e. echocardiogram and laboratory results) are negative and (3) the diagnosis remains uncertain. Choices have to be made about implantation of pacemaker (PM), implantable cardioverter/defibrillator (ICD) or ambulatory additional work-up. In case there are no indications for PM or ICD the patient can be discharged with the possibility of additional short- or long-term ECG monitoring if arrhythmogenic syncope is still suspected. The choice of short-term or long-term ECG monitoring depends on the likelihood and time frame of recurrence.
Holter monitoring It is important to make two important statements about short-term ECG monitoring. First, the efficacy of traditional Holter monitoring systems depends on the rate of symptom recurrence. If there are infrequent episodes or isolated events, the likelihood of establishing a symptom–ECG correlation by Holter monitoring is very low. Second, prospective event recorders used for investigations of palpitations are not indicated for diagnosing syncope since they cannot give information of the ECG rhythm at the time of syncope. The Holter monitor routinely provides 24–72 hours of continuously ECG monitoring typically by 3 leads (or 12 leads). The diagnostic yield is low because recurrences are, as mentioned, not likely to appear within that short time span. In an early but very large study of 24-hour Holter monitoring in 1512 patients referred for syncope, Gibson and Heitzman22 found that 0.5% (7/1,512) had arrhythmic syncope while 15% had
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Table 3 – Baseline ECG features suggesting arrhythmogenic syncope. Ventricular tachycardia Bundle branch block (QRS duration ≥ 120 ms) Sinoatrial block Atrioventricular block Sinus bradycardia (in physically untrained) Short-or long-QT intervals Brugada syndrome (right bundle branch block with ST-elevation in lead V1–V3 Negative T wave in right precordial leads and epsilon waves arrhythmogenic right ventricular dysplasia Supraventricular tachycardia Adapted from the ESC guidelines.11
symptoms (pre-syncope and syncope) without any arrhythmia correlation. In one study pooling results from Holter and external loop recorders (ELR), 4% of the patients had an arrhythmia diagnosed as a cause of symptoms within a 72hour period, whereas, again, 15% of the patients had symptoms without any arrhythmias. The overall yield of all electrocardiographic abnormalities in that study was 22% at 48 hours.23 In an older smaller study by Bass et al.24 15% of the syncope patients had major ECG abnormalities, but again only one (1%) patient was symptomatic during the monitoring period. By increasing the duration of monitoring from 24 to 48 hours an increasing number of ECG abnormalities were detected and consequently also a higher diagnostic yield. On the contrary, they found that 3 days of Holter monitoring did not provide significant additional diagnostic information in these patients.24,25 Kühne et al.26 reported the use of 24-hour Holter monitoring in 475 elderly syncope patients with a median age of 84 years. They found relevant cardiac arrhythmias and diagnostic for syncope in 11%, while 10% had symptoms without any significant arrhythmia.
A common factor when reporting the diagnostic yield is that symptoms without ECG correlations (i.e. a negative diagnostic evaluation) are counted as diagnostic. This results in higher diagnostic yields as compared to only reporting symptom–rhythm correlation diagnostic yields. In short, the likelihood of establishing a symptom–ECG “positive” correlation with a Holter monitoring device is very low, while a symptom–ECG “negative” correlation seems to be in the range of 10%–20%. However, as described later, presyncope may not be an accurate surrogate marker for syncope. The advantages of Holter monitoring include its availability, low complexity of use for patients and staff and a low perpatient cost. The disadvantages include the high cost per diagnosis and the limited period of use. In conclusion, Holter monitoring should be limited to patients with a very high short-term probability of arrhythmias and/or patients with frequent symptoms.
External loop recording/R-test/event recording The ELR allows for a monitoring period of up to 6 weeks. Unlike the Holter system with continuous ECG recordings, the ELR saves data if manually activated or if automatically activated by the device. They are based on a loop memory system that continuously records and deletes ECGs. The capacities, mode of data transmission, tachycardia and bradycardia algorithms vary significantly depending on the manufacturer. When activated by the patient, post-syncope, the ELR records typically 1–15 minutes pre-activation ECG and 1–5 minutes post-activation ECG. The diagnostic yield increases dramatically according to the time frame of use. Four studies have investigated the diagnostic yield of the ELR (Table 4) and the symptom–rhythm correlation. Gula et al.27 reported data from 78 patients from the Comparison Of Loop Recorders Against Holter in Patients with Syncope (COLAPS)
Table 4 – The diagnostic yield of Holter and external loop recorders in selected studies.
Setting Unexplained recurrent syncope. HOLTER Unexplained syncope. HOLTER arm Unexplained syncope. HOLTER Unexplained syncope ≥ 80 years of age. HOLTER Unexplained syncope. ELR arm Unexplained recurrent syncope and neg. tilt-table test. ELR Unexplained syncope. ELR
Source Gibson et al.
Syncope During Monitor With ECG Abnormalities 7/1512 (0.5%)
Period
Pre-syncope or Syncope Asymptomatic Without ECG Diagnostic “Major” ECG Abnormalities Yield Abnormalities
24 hours
225/1512 (15%)
15%
More than 40%
Sivakumaran et al. 0/51 (0%)
48 hours
12/55 (22%)
22%
NR
Bass et al.
1/95 (1%)
24 hours
13/95 (14%)
14%
14/95 (15%)
Kühne et al.
NR/475
24 hours
46/475 (10%)
17%
53/475 (11%) a
Sivakumaran et al. 1/78 (1%)
1 month
44/78 (56%)
56%
NA
Schuchert et al.
1/24 (4%)
8 weeks
8/24 (33%)
38%
NA
Linzer et al.
7/57 (12%)
1 month
7/57 (12%)
25%
NA
Abbreviations: NR, not reported; NA, not applicable. a In this study the 53 major ECG abnormalities were considered diagnostic of the initial syncope.
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trial and found that a diagnosis was made in 21% at 48 hours, 50% at 15 days, and 90% at 33 days. In this study 56% had symptoms (both pre-syncope and syncope) without a definite arrhythmia being detected (negative symptom–ECG correlation), while only one patient in this study had significant arrhythmia during symptoms (positive symptom–ECG correlation).23 In a small study by Schuchert et al.28 24 patients with recurrent syncope and negative tilt-table test were enrolled. One patient experienced syncope during monitoring and only 17% (4/24) had syncope during an average of 15 months of follow-up after termination of the monitoring. In one of the earliest reports on the use of ELR, Linzer et al.29 described that arrhythmic ECG documentation (positive or negative) was present in 25% (14/57) of the syncopal events (both pre-syncope and syncope) during 30 days of monitoring in patients with many recurrences. A frequent characteristic of ELR was that a high proportion (up to 50%) of patients failed to wear the device or activate it properly at the time of symptoms. These cited studies varied significantly in the characteristics of patients included and the number of syncope episodes leading up to inclusion in the studies. A Mobile Cardiac Outpatient Telemetry (MCOT) device records ECG continuously and incorporates algorithms for automatic arrhythmia detection and uses wireless (real-time) transmission to a service center. In a randomized study comparing MCOT with traditional ELR Rothman et al.30 found that in a subgroup of patients with syncope, MCOT had a greater diagnostic yield and a shorter time to diagnosis. Further studies are needed to evaluate the efficacy of automatized remote telemetry in the work-up of unexplained syncope. Recently the diagnostic utility of a leadless 14-day ambulatory adhesive patch was described and it seems to have both high patient compliance and feasible arrhythmia detection, although it does not have wireless transmission capabilities. A total of 4029 patients wore the patch in the study, but the initial results did not report specifically for syncope patients and the utility in comparison with ELR and ILR is uncertain at present time.31 The major limitations in the use of ELR are patient compliance, failure to operate the device properly and difficulties handling cutaneous patch electrodes. A costeffectiveness analysis has indicated that the marked improvement in diagnostic yield offsets the cost of the ELR and that they are an economically attractive alternative when compared to Holter monitoring.32 In the Randomized Assessment of Syncope Trial (RAST) Krahn et al.33 randomized 60 patients to a strategy of either “conventional investigation” with an ELR for 2–4 weeks, a electrophysiological testing and a tilt-table test versus a “prolonged monitoring” for 1 year with an ILR. This study suggested that early implantation with ILR was more efficacious (52% diagnosed versus 20%) and more cost-effective than the “conventional” strategy.33 In conclusion the use of ELR is more cost-effective than the Holter but less cost-effective than the ILR as it is limited by the rate of syncopal recurrences. The negative diagnostic (no symptom–ECG correlation) value of the ELR is however very important, they are superior to Holter monitoring as an initial strategy and the role of MCOT and other variants are still to be defined.
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Implantable loop recorders ILRs were developed in the early 1990s and are small (≈60 mm × 20 mm; 15 g) devices that are implanted subcutaneously in the left frontal pectoral region as an outpatient procedure. Currently there are two FDA-approved ILRs available for clinical use. The REVEAL PLUS (Medtronic, Minneapolis, USA) and the CONFIRM (St Jude, St Paul, USA). With improving technology they now have a battery life of approximately 3 years and are able to detect a bipolar ECG signal from small leads on either end of the device. Events can be detected manually or by automatized algorithms and are saved on a solid-state memory up to 40 minutes before and 1–5 minutes after activation. Many observational smaller studies have investigated the use of the ILR with considerable variation. The RAST33 study investigated the use of an ILR compared to a conventional strategy as noted above. In the large multinational Place of Reveal In the Care pathway and Treatment of patients with Unexplained Recurrent Syncope (PICTURE) registry study an ILR-guided diagnosis was demonstrated in 78% of 570 patients with pre-syncope or syncope during an average follow-up of 10 months and 38% (218/570) had documented syncope within this period.34 In patients with recurrent neurally mediated syncope, in contrast to tilt-table testing, the ILR also provides information about the characteristics of the heart rhythm during recurrent syncope35,36 and may help guide decisions regarding specific therapy as previously mentioned.18,35,37 The ISSUE studies gave important understandings of the mechanism and treatment of syncope by the use of ILR. In ISSUE-1, three distinct syncope groups were investigated revealing three novel insights on mechanism: The first group consisted of 35 patients with structural heart disease, reduced ejection fraction and negative electrophysiological study. During a mean follow-up of 6 months, 17% (6/35) patients had recurrence and investigation of the device revealed that (unexpectedly) none of these were due to ventricular tachycardia.13 The second group consisted of 52 patients with bundle branch block and negative electrophysiological study.38 Syncope recurred in 42% (22/52) and most events were due to complete heart block or other block variants. Only 4% in this group had syncope without a significant arrhythmia. In the last group, 111 patients with the absence of structural heart disease and with a normal ECG, had tilt-table tests performed. A total of 34% (38/111) of the patients had recurrence and there was a symptom–ECG correlation in 84% (32/38). Approximately 50% of the patients in this group had one or more prolonged asystolic episodes and the authors concluded that most of these patients had reflex (neutrally mediated) cardioinhibitory syncope. Furthermore there was no good correlation between pre-syncope symptoms and significant arrhythmias recorded by the ILR,12 essentially ruling out pre-syncope as a surrogate marker for arrhythmic true syncope. In the second ISSUE study, ISSUE-2, 392 patients with recurrent suspected neurally mediated syncope were enrolled. During a median follow-up of 9 months, 26% (103/
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392) experienced recurrence. Of these patients 46% (47/103) had asystole during the event and received a pacemaker (PM). This therapeutic intervention with PM reduced the risk of subsequent syncope by 80% when compared to those who did not receive the PM.18 There were concerns however, of a placebo effect of PM implantation.39 In ISSUE-3 which was comparable to ISSUE-2 except for a double-blind approach at time of PM implantation, patients were randomized to pacemaker activated on or off with blinding of patient and physician. A total of 511 patients were implanted with an ILR and dual-chamber permanent pacing was found effective in reducing the relative risk of recurrence of syncope by 57% in patients above the age of 40 years with asystolic neurally mediated syncope. This study supports both early implantation of ILR and subsequent invasive treatment for the otherwise usually benign neurally mediated syncope.40 However, even in this selected asystolic patient category treated with a PM a significant proportion (25%) of the patients continued to faint and the number needed to treat may still be relatively high. The role of the ILR-guided treatment in relatively high-risk patients (bifascicular block, preserved ejection fraction and syncope in patients above the age of 80 years) is currently being examined in the Syncope: Pacing or Recording in ThE Later Years (SPRITELY) study.41 The diagnostic yield of the ILR is indisputable higher than both Holter and ELR due to prolonged monitoring period. In pooled data comprising 506 patients the symptom–ECG correlation was shown in 35% (176/501), only 33% of these were negative diagnostic (symptoms without arrhythmias).11-13,38 In highly selected patients the symptom–ECG correlation was as high as 88%42 and the diagnostic value increased with increasing observation time. Furukawa et al.43 found estimated cumulative diagnostic rates of 30%, 43%, 52%, and 80% at 1, 2, 3, and 4 years of ILR observation time.
Where the ILR is in the work-up? Current European Society of Cardiology guidelines recommend ILR implantation at an early stage in patients with unexplained syncope without high-risk criteria based on efficacy, safety and cost–utility (class I, level A).11,44 This is in line with the above cited limited diagnostic utility of shortterm ECG monitoring.45 An ILR also yields valuable and therapeutic information in unexplained syncope in high-risk patients in whom otherwise comprehensive evaluations have not revealed the cause (class I, level B). Further in older (above 50 years) patients with possible frequent neutrally mediated syncope ILR may be indicated to guide pacemaker therapy for selected asystolic and bradycardic events (class IIA, level B). Lastly ILR also seems plausible for patients when the diagnosis of syncope has not yet been established in selected elderly patients with a history of falls or patients with depression and unexplained loss of consciousness46,47 (class 2B, level C). ILRs should not be used in low-risk patients, unless they have a clear diagnostic or therapeutic purpose. The disadvantages of ILR include the need for a minor surgical procedure, the difficulty of not always being able to differentiate supraventricular from ventricular arrhythmias,
the presence of under- or over-sensing that may exhaust the memory of the ILR, and the initial cost of the device.
ECG diagnosis In summary, a diagnosis can be made if there is a correlation between syncope or pre-syncope and a detected arrhythmia. In the absence of symptom–ECG correlation, ventricular pauses ≥3 s or periods of Mobitz type II atrioventricular block, third-degree atrioventricular block or ventricular tachycardia are arrhythmias that lead to a very plausible cause of the initial syncope as well as a specific treatment. In the absence of an arrhythmia at the time of syncope (but no presyncope), ECG monitoring may exclude arrhythmias as the cause of syncope. Guidelines have adapted the ISSUE classification and definition of rhythm disturbances recorded with the ILR at the time of syncope.11,48
Asymptomatic arrhythmias found during ECG monitoring Asymptomatic arrhythmias are often clinically relevant in decision making for arrhythmia diagnosis and treatment. Auto-activation and detection of arrhythmias aid the clinician, but also provide grounds for questions. Holter, MCOT and ILR monitoring suggests that asymptomatic arrhythmias are quite common in elderly patients with or without syncope and in patients with or without cardiac disease.49-53 It is reasonable to assume that patients with an arrhythmic cause of syncope will also have episodes that do not meet the above-mentioned arrhythmic thresholds to cause symptoms. Detection of asymptomatic marked bradycardia or tachycardia, however, often influences clinician decisions to treat these findings to prevent recurrent syncope, most likely resulting in excessive treatment.
Summary This review explores the evidence and roles of short-term (Holter and ELR) and long-term (ILR) ECG monitoring. After proper risk stratification, in low- or intermediate-risk patients short-term Holter monitoring is reserved for the very few patients in whom syncope is expected to recur within a week, while external loop recorders can be used when syncope is expected to recur within 1 month. In patients, where an arrhythmic cause is suspected but the likelihood of recurrence is low, early use of an implantable loop recorder is recommended and might become the reference standard. The investigations performed in syncope are based on a clinical probability analysis, and the choice of diagnostic testing is predicated upon the results of the initial tests. Therefore the indications and use of ECG monitoring in the work-up of unexplained syncope, in particular, continue to be a debatable subject. A thoughtful and targeted approach with mechanismspecific treatment and guideline-adherent strategy reduces
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health care costs and improves the selection of patients for optimal treatment possibilities.
Statement of Conflict of Interest
15.
16.
M.H.R. has no conflict of interest to disclose. W.Z. has received grants from Boston. 17. REFERENCES
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of unknown origin: implications from a large syncope database. Ann Noninvasive Electrocardiol. 2009;14(2):119-27. Farwell DJ, Freemantle N, Sulke N. The clinical impact of implantable loop recorders in patients with syncope. Eur Heart J. 2006;27(3):351-6. Ungar A, Del Rosso A, Giada F, Bartoletti A, Furlan R, Quartieri F, et al. Early and late outcome of treated patients referred for syncope to emergency department: the EGSYS 2 follow-up study. Eur Heart J. 2010;31(16):2021-6. Brignole M, Hamdan MH. New concepts in the assessment of syncope. J Am Coll Cardiol. 2012;59(18):1583-91. Brignole M, Sutton R, Menozzi C, Garcia-Civera R, Moya A, Wieling W, et al. Early application of an implantable loop recorder allows effective specific therapy in patients with recurrent suspected neurally mediated syncope. Eur Heart J. 2006;27(9):1085-92. Shen WK, Decker WW, Smars PA, Goyal DG, Walker AE, Hodge DO, et al. Syncope Evaluation in the Emergency Department Study (SEEDS): a multidisciplinary approach to syncope management. Circulation. 2004;110(24):3636-45. Shen WK, Traub SJ, Decker WW. Syncope management unit: evolution of the concept and practice implementation. Prog Cardiovasc Dis. 2013;55(4):382-9. Croci F, Brignole M, Alboni P, Menozzi C, Raviele A, Del Rosso A, et al. The application of a standardized strategy of evaluation in patients with syncope referred to three syncope units. Europace. 2002;4(4):351-5. Gibson TC, Heitzman MR. Diagnostic efficacy of 24-hour electrocardiographic monitoring for syncope. Am J Cardiol. 1984;53(8):1013-7. Sivakumaran S, Krahn AD, Klein GJ, Finan J, Yee R, Renner S, et al. A prospective randomized comparison of loop recorders versus Holter monitors in patients with syncope or presyncope. Am J Med. 2003;115(1):1-5. Bass EB, Curtiss EI, Arena VC, Hanusa BH, Cecchetti A, Karpf M, et al. The duration of Holter monitoring in patients with syncope. Is 24 hours enough? Arch Intern Med. 1990;150(5): 1073-8. Arya A, Haghjoo M, Khosrawi A, Emkanjoo Z, Sadr-Ameli MA. Predictors of arrhythmic events during second day monitoring in patients with normal first day Holter recordings. Indian Heart J. 2005;57(3):241-4. Kühne M, Schaer B, Sticherling C, Osswald S. Holter monitoring in syncope: diagnostic yield in octogenarians. J Am Geriatr Soc. Jul 2011;59(7):1293-8. Gula LJ, Krahn AD, Massel D, Skanes A, Yee R, Klein GJ. External loop recorders: determinants of diagnostic yield in patients with syncope. Am Heart J. 2004;147(4):644-8. Schuchert A, Maas R, Kretzschmar C, Behrens G, Kratzmann I, Meinertz T. Diagnostic yield of external electrocardiographic loop recorders in patients with recurrent syncope and negative tilt table test. Pacing Clin Electrophysiol. 2003;26(9): 1837-40. Linzer M, Pritchett EL, Pontinen M, McCarthy E, Divine GW. Incremental diagnostic yield of loop electrocardiographic recorders in unexplained syncope. Am J Cardiol. 1990;66(2): 214-9. Rothman SA, Laughlin JC, Seltzer J, Walia JS, Baman RI, Siouffi SY, et al. The diagnosis of cardiac arrhythmias: a prospective multi-center randomized study comparing mobile cardiac outpatient telemetry versus standard loop event monitoring. J Cardiovasc Electrophysiol. Mar 2007;18(3): 241-7. Turakhia MP, Hoang DD, Zimetbaum P, Miller JD, Froelicher VF, Kumar UN, Xu X, et al. Diagnostic Utility of a Novel Leadless Arrhythmia Monitoring Device. Am J Cardiol. May 11 2013.
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32. Rockx MA, Hoch JS, Klein GJ, Yee R, Skanes AC, Gula LJ, et al. Is ambulatory monitoring for “community-acquired” syncope economically attractive? A cost-effectiveness analysis of a randomized trial of external loop recorders versus Holter monitoring. Am Heart J. 2005;150(5):1065. 33. Krahn AD, Klein GJ, Yee R, Skanes AC. Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy. Circulation. 2001;104(1):46-51. 34. Edvardsson N, Frykman V, van Mechelen R, Mitro P, MohiiOskarsson A, Pasquie JL, et al. Use of an implantable loop recorder to increase the diagnostic yield in unexplained syncope: results from the PICTURE registry. Europace. 2011;13(2):262-9. 35. Brignole M, Sutton R, Menozzi C, Garcia-Civera R, Moya A, Wieling W, et al. Lack of correlation between the responses to tilt testing and adenosine triphosphate test and the mechanism of spontaneous neurally mediated syncope. Eur Heart J. 2006;27(18):2232-9. 36. Deharo JC, Jego C, Lanteaume A, Djiane P. An implantable loop recorder study of highly symptomatic vasovagal patients: the heart rhythm observed during a spontaneous syncope is identical to the recurrent syncope but not correlated with the head-up tilt test or adenosine triphosphate test. J Am Coll Cardiol. 2006;47(3):587-93. 37. Hong P, Sulke N. Implantable diagnostic monitors in the early assessment of syncope and collapse. Prog Cardiovasc Dis. 2013;55(4):410-7. 38. Brignole M, Menozzi C, Moya A, Garcia-Civera R, Mont L, Alvarez M, et al. Mechanism of syncope in patients with bundle branch block and negative electrophysiological test. Circulation. 2001;104(17):2045-50. 39. Sud S, Massel D, Klein GJ, Leong-Sit P, Yee R, Skanes AC, et al. The expectation effect and cardiac pacing for refractory vasovagal syncope. Am J Med. 2007;120(1):54-62. 40. Brignole M, Menozzi C, Moya A, Andresen D, Blanc JJ, Krahn AD, et al. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial. Circulation. 2012;125(21):2566-71. 41. Krahn AD, Morillo CA, Kus T, Manns B, Rose S, Brignole M, et al. Empiric pacemaker compared with a monitoring strategy in patients with syncope and bifascicular conduction block–rationale and design of the Syncope: Pacing or Recording in ThE Later Years (SPRITELY) study. Europace. 2012;14(7):1044-8. 42. Solano A, Menozzi C, Maggi R, Donateo P, Bottoni N, Lolli G, et al. Incidence, diagnostic yield and safety of the implantable loop-recorder to detect the mechanism of syncope in patients with and without structural heart disease. Eur Heart J. 2004;25(13):1116-9.
43. Furukawa T, Maggi R, Bertolone C, Fontana D, Brignole M. Additional diagnostic value of very prolonged observation by implantable loop recorder in patients with unexplained syncope. J Cardiovasc Electrophysiol. 2012;23(1):67-71. 44. Brignole M, Vardas P, Hoffman E, Huikuri H, Moya A, Ricci R, et al. Indications for the use of diagnostic implantable and external ECG loop recorders. Europace. 2009;11(5):671-87. 45. Krahn AD, Andrade JG, Deyell MW. Selecting appropriate diagnostic tools for evaluating the patient with syncope/collapse. Prog Cardiovasc Dis. 2013;55(4):402-9. 46. Pezawas T, Stix G, Kastner J, Schneider B, Wolzt M, Schmidinger H. Implantable loop recorder in unexplained syncope: classification, mechanism, transient loss of consciousness and role of major depressive disorder in patients with and without structural heart disease. Heart. 2008;94(4):e17. 47. Armstrong VL, Lawson J, Kamper AM, Newton J, Kenny RA. The use of an implantable loop recorder in the investigation of unexplained syncope in older people. Age Ageing. 2003;32(2):185-8. 48. Brignole M, Moya A, Menozzi C, Garcia-Civera R, Sutton R. Proposed electrocardiographic classification of spontaneous syncope documented by an implantable loop recorder. Europace. 2005;7(1):14-8. 49. Gang UJ, Jons C, Jorgensen RM, Abildstrom SZ, Messier MD, Haarbo J, et al. Clinical significance of late high-degree atrioventricular block in patients with left ventricular dysfunction after an acute myocardial infarction—a Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) substudy. Am Heart J. 2011;162(3):542-7. 50. Jons C, Jacobsen UG, Joergensen RM, Olsen NT, Dixen U, Johannessen A, et al. The incidence and prognostic significance of new-onset atrial fibrillation in patients with acute myocardial infarction and left ventricular systolic dysfunction: a CARISMA substudy. Heart Rhythm. 2011;8(3): 342-8. 51. Hindricks G, Pokushalov E, Urban L, Taborsky M, Kuck KH, Lebedev D, et al. Performance of a new leadless implantable cardiac monitor in detecting and quantifying atrial fibrillation: results of the XPECT trial. Circ Arrhythm Electrophysiol. 2010;3(2):141-7. 52. Engel JM, Mehta V, Fogoros R, Chavan A. Study of arrhythmia prevalence in NUVANT Mobile Cardiac Telemetry system patients. Conf Proc IEEE Eng Med Biol Soc. 2012;2012:2440-3. 53. Roche F, Gaspoz JM, Da Costa A, Isaaz K, Duverney D, Pichot V, et al. Frequent and prolonged asymptomatic episodes of paroxysmal atrial fibrillation revealed by automatic long-term event recorders in patients with a negative 24-hour Holter. Pacing Clin Electrophysiol. 2002;25(11):1587-93.
Available online at www.sciencedirect.com
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ECG Monitoring in Syncope Martin H. Ruwald⁎, Wojciech Zareba Cardiology Division, Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, NY, USA
A R T I C LE I N F O
AB ST R A C T
Keywords:
Electrocardiographic (ECG) monitoring is a well-established procedure in the work-up of
Syncope
patients with syncope or for diagnosing arrhythmias. The investigation of syncope remains,
ECG monitoring
however, challenging and physicians have an increasing armamentarium of diagnostic
Diagnosis
tools available and with advances in technology the role of these tools has to be
Risk stratification
continuously evaluated. The gold standard for the diagnosis of syncope is a symptom– ECG correlation, and while many studies have investigated the use and indications of both short-term and long-term monitoring; there is still some uncertainty in their clinical utility and practical approach. The use of ECG monitoring and other diagnostic tools is often subject to a “shot-gun approach” rather than a strict guideline algorithm. A systematic approach and selection of ECG monitoring tools helps permit an effective usage of the limited health care resources available for the management of unexplained syncope. In this review we aim to focus and clarify the role of short-term (Holter and external loop recorders) and long-term (implantable loop recorders) ECG monitoring in the diagnosis and management of patients with unexplained syncope. © 2013 Elsevier Inc. All rights reserved.
Syncope and recurrent syncope are frequent causes of hospitalization and they remain common problems in the general population.1,2 The etiological diagnosis and assessment of syncope is challenging for the physician due to the unpredictability of the symptom, the unknown rate of recurrence and the short- and long-term risks associated with the variable causes of the syncope. The prognosis in syncope varies markedly with both underlying comorbidities and the etiological causality of the syncopal event. 2-8 The initial investigations (history, physical examination, ECG and orthostatic blood pressure measurements) can provide the diagnosis in up to 50% of the cases. 9,10 When the diagnosis is made no further testing is usually needed and appropriate therapy can be applied. For the remaining cases where the diagnosis is uncertain, the risk assessment and
suspected etiology of the syncope determine the further diagnostic approach (Fig 1). The criteria to determine whether the patient is at short- or long-term high-risk or low-risk is covered extensively in the European Society of Cardiology guidelines from 200911 and has been evaluated by several studies from emergency departments and are referenced here in Table 1.11 If arrhythmogenic syncope is suspected in high-risk patients, the patient should be evaluated with inpatient telemetry for 24–72 hours. If arrhythmogenic syncope is suspected and the patient is determined to be at low- or intermediate-risk, short- or longterm ECG monitoring can be applied depending on expected rate of recurrence. When is arrhythmogenic syncope suspected? The clinical features suggesting arrhythmogenic syncope includes synco-
Statement of Conflict of Interest: see page 209. ⁎ Address reprint requests to Martin H. Ruwald, MD, PhD, Heart Research Follow-up Program, University of Rochester Medical Center, 265 Crittenden Boulevard, Rochester, NY 14642. E-mail address: [email protected] (M.H. Ruwald). 0033-0620/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pcad.2013.08.007
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Abbreviations and Acronyms
pe while supine or on exertion, palpitations ECG = electrocardiogram prior to syncope, ECG ELR = external loop recorder abnormalities at the initial evaluation, the ICD = implantable cardioverter/ presence of structural defibrillator heart disease and a ILR = implantable loop recorder family history of sudden death (Tables 2 MCOT = mobile cardiac outpaand 3). This review tient telemegtry focuses on the use and indications of ECG monitoring in the evaluation of a patient with syncope based on the current evidence.
Electrocardiographic monitoring ECG monitoring is the method of choice for establishing symptom–ECG correlation and is considered the gold standard for diagnosing arrhythmogenic syncope. The diagnostic approach therefore involves varying durations of monitoring intervals in the hope of obtaining this important correlation. In this context it is important to remember that cardioinhibitory reflex (neutrally mediated) syncope also presents itself as an arrhythmia (most often asystole) when monitored by ECG.12,13 Abnormal ECGs are also well correlated with brady- or/and tachyarrhythmic causes of syncope when these patients are evaluated by an electrophysiologic
study.14 Thus mechanism and etiology of syncope do not always correlate. Similar mechanisms of syncope are present in various etiologies, and all etiologic manifestations can cause syncope by different mechanisms, that is, bradycardia or asystole in both vasovagal and cardiac etiology. This fact has led to studies investigating efficacy of treatment by mechanism. In the Eastbourne Syncope Assessment Study (EaSyAS),15 patients with an implantable loop recorder (ILR) leading to an ECG-directed specific treatment had a significant reduction of syncope recurrences. On the other hand the syncopal recurrence rate did not differ among subgroups in the Evaluation of Guidelines in SYncope Study 2 (EGSYS 2) where treatment was based on the established syncopal etiology.16 Since there is a therapeutic consequence in establishing the causal mechanism rather than the causal pathophysiological etiology (i.e. permanent cardiac pacing when documented asystolic pauses are present in vasovagal (neutrally mediated) syncope),this may be the most appropriate approach when evaluating syncope by means of electrocardiographic monitoring systems.17 As many as 50% of all syncopal events in patients with no apparent heart disease present as arrhythmias when the patients have been subject to investigations with implantable loop recorder (ILR).12,18 If the patient experiences a recurrence while monitored and no symptom–ECG correlation was evident, this allows for elimination of an arrhythmogenic mechanism. However during the period of monitoring, many asymptomatic arrhythmias are also recorded and how should those be dealt with? Finally there is the potential for serious
Fig 1 – The use of ECG monitoring in the work-up of syncope.
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Table 1 – Risk markers in unselected patients with syncope. Scheme
Clinical Markers
Short-term risk San Francisco Syncope Abnormal ECG Rule Low blood pressure Heart failure Shortness of breath Hematocrit less than 30% STePS Abnormal ECG Trauma at syncope No warning of syncope Male sex ROSE rule Abnormal ECG Elevated BNP levels Chest pain Fecal blood Long-term risk OESIL score Abnormal ECG Age above 65 years History of cardiovascular disease No warning of syncope Martin et al. Abnormal ECG Heart failure Shortness of breath Age above 45 years Ventricular arrhythmia EGSYS score Abnormal ECG Palpitations prior to syncope History of cardiovascular disease Syncope during exertion or while supine
injury or death during this “passive” monitoring period so the selection of patients has to be precise so as to avoid fatal outcomes. These are concerning issues in the current management of syncope patients during the period of ECG monitoring.
Selection of patients for telemetry during inpatient hospitalization For short-term high-risk patients suspected of arrhythmiogenic syncope (essentially all high-risk patients at risk of sudden cardiac death or major cardiac events) current guidelines recommend prompt hospitalization.11 Essentially the factors associated with short-term high risks are very similar to the factors associated with high probability of arrhythmogenic syncope and factors associated with short-
Table 2 – Baseline clinical features suggesting arrhythmogenic syncope. Syncope during exercise or in a supine position Palpitations prior to or at the time of syncope A family history of sudden death A history of cardiac disease (heart failure, low ejection fraction or previous myocardial infarction) Adapted from the ESC guidelines.11
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term adverse outcome in the risk stratification studies from emergency department (a combination of Tables 1 and 2). A necessity for prompt hospitalization and telemetry could therefore also include patients where the initial ECG shows features suggesting a high-risk despite a history and/or physical examination that is negative or seems to be low risk. Such conditions include but are not limited to the Brugada syndrome, short- and long-QT syndrome, arrhythmogenic right ventricular dysplasia, high-degree atrioventricular block and ventricular tachycardia.11 In the randomized Syncope Evaluation in the Emergency Department Study (SEEDS)19 a novel syncope unit significantly improved the diagnostic yield in the emergency department and reduced hospital admissions without affecting recurrent syncope or all-cause mortality for patients with intermediate risk. These findings provided benchmark results for optimizing and improving patient care and effectively utilizing healthcare resources. Syncope units and specialized care pathways for syncope patients have unfortunately not yet been widely implemented.20 Telemetry is usually performed from 24 to 72 hours, but currently no data support a specific duration for telemetry. Telemetry and admission are warranted due to high shortterm risk of sudden cardiac death, or ventricular arrhythmias even though the diagnostic yield may be rather low (16%) even in these pre-selected patients.21 Basically, however, no studies have investigated the value of in-hospital ECG monitoring of syncope in high-risk patients if (1) telemetry proves unhelpful in the diagnostic progress, (2) other inhospital diagnostic approaches (i.e. echocardiogram and laboratory results) are negative and (3) the diagnosis remains uncertain. Choices have to be made about implantation of pacemaker (PM), implantable cardioverter/defibrillator (ICD) or ambulatory additional work-up. In case there are no indications for PM or ICD the patient can be discharged with the possibility of additional short- or long-term ECG monitoring if arrhythmogenic syncope is still suspected. The choice of short-term or long-term ECG monitoring depends on the likelihood and time frame of recurrence.
Holter monitoring It is important to make two important statements about short-term ECG monitoring. First, the efficacy of traditional Holter monitoring systems depends on the rate of symptom recurrence. If there are infrequent episodes or isolated events, the likelihood of establishing a symptom–ECG correlation by Holter monitoring is very low. Second, prospective event recorders used for investigations of palpitations are not indicated for diagnosing syncope since they cannot give information of the ECG rhythm at the time of syncope. The Holter monitor routinely provides 24–72 hours of continuously ECG monitoring typically by 3 leads (or 12 leads). The diagnostic yield is low because recurrences are, as mentioned, not likely to appear within that short time span. In an early but very large study of 24-hour Holter monitoring in 1512 patients referred for syncope, Gibson and Heitzman22 found that 0.5% (7/1,512) had arrhythmic syncope while 15% had
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Table 3 – Baseline ECG features suggesting arrhythmogenic syncope. Ventricular tachycardia Bundle branch block (QRS duration ≥ 120 ms) Sinoatrial block Atrioventricular block Sinus bradycardia (in physically untrained) Short-or long-QT intervals Brugada syndrome (right bundle branch block with ST-elevation in lead V1–V3 Negative T wave in right precordial leads and epsilon waves arrhythmogenic right ventricular dysplasia Supraventricular tachycardia Adapted from the ESC guidelines.11
symptoms (pre-syncope and syncope) without any arrhythmia correlation. In one study pooling results from Holter and external loop recorders (ELR), 4% of the patients had an arrhythmia diagnosed as a cause of symptoms within a 72hour period, whereas, again, 15% of the patients had symptoms without any arrhythmias. The overall yield of all electrocardiographic abnormalities in that study was 22% at 48 hours.23 In an older smaller study by Bass et al.24 15% of the syncope patients had major ECG abnormalities, but again only one (1%) patient was symptomatic during the monitoring period. By increasing the duration of monitoring from 24 to 48 hours an increasing number of ECG abnormalities were detected and consequently also a higher diagnostic yield. On the contrary, they found that 3 days of Holter monitoring did not provide significant additional diagnostic information in these patients.24,25 Kühne et al.26 reported the use of 24-hour Holter monitoring in 475 elderly syncope patients with a median age of 84 years. They found relevant cardiac arrhythmias and diagnostic for syncope in 11%, while 10% had symptoms without any significant arrhythmia.
A common factor when reporting the diagnostic yield is that symptoms without ECG correlations (i.e. a negative diagnostic evaluation) are counted as diagnostic. This results in higher diagnostic yields as compared to only reporting symptom–rhythm correlation diagnostic yields. In short, the likelihood of establishing a symptom–ECG “positive” correlation with a Holter monitoring device is very low, while a symptom–ECG “negative” correlation seems to be in the range of 10%–20%. However, as described later, presyncope may not be an accurate surrogate marker for syncope. The advantages of Holter monitoring include its availability, low complexity of use for patients and staff and a low perpatient cost. The disadvantages include the high cost per diagnosis and the limited period of use. In conclusion, Holter monitoring should be limited to patients with a very high short-term probability of arrhythmias and/or patients with frequent symptoms.
External loop recording/R-test/event recording The ELR allows for a monitoring period of up to 6 weeks. Unlike the Holter system with continuous ECG recordings, the ELR saves data if manually activated or if automatically activated by the device. They are based on a loop memory system that continuously records and deletes ECGs. The capacities, mode of data transmission, tachycardia and bradycardia algorithms vary significantly depending on the manufacturer. When activated by the patient, post-syncope, the ELR records typically 1–15 minutes pre-activation ECG and 1–5 minutes post-activation ECG. The diagnostic yield increases dramatically according to the time frame of use. Four studies have investigated the diagnostic yield of the ELR (Table 4) and the symptom–rhythm correlation. Gula et al.27 reported data from 78 patients from the Comparison Of Loop Recorders Against Holter in Patients with Syncope (COLAPS)
Table 4 – The diagnostic yield of Holter and external loop recorders in selected studies.
Setting Unexplained recurrent syncope. HOLTER Unexplained syncope. HOLTER arm Unexplained syncope. HOLTER Unexplained syncope ≥ 80 years of age. HOLTER Unexplained syncope. ELR arm Unexplained recurrent syncope and neg. tilt-table test. ELR Unexplained syncope. ELR
Source Gibson et al.
Syncope During Monitor With ECG Abnormalities 7/1512 (0.5%)
Period
Pre-syncope or Syncope Asymptomatic Without ECG Diagnostic “Major” ECG Abnormalities Yield Abnormalities
24 hours
225/1512 (15%)
15%
More than 40%
Sivakumaran et al. 0/51 (0%)
48 hours
12/55 (22%)
22%
NR
Bass et al.
1/95 (1%)
24 hours
13/95 (14%)
14%
14/95 (15%)
Kühne et al.
NR/475
24 hours
46/475 (10%)
17%
53/475 (11%) a
Sivakumaran et al. 1/78 (1%)
1 month
44/78 (56%)
56%
NA
Schuchert et al.
1/24 (4%)
8 weeks
8/24 (33%)
38%
NA
Linzer et al.
7/57 (12%)
1 month
7/57 (12%)
25%
NA
Abbreviations: NR, not reported; NA, not applicable. a In this study the 53 major ECG abnormalities were considered diagnostic of the initial syncope.
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trial and found that a diagnosis was made in 21% at 48 hours, 50% at 15 days, and 90% at 33 days. In this study 56% had symptoms (both pre-syncope and syncope) without a definite arrhythmia being detected (negative symptom–ECG correlation), while only one patient in this study had significant arrhythmia during symptoms (positive symptom–ECG correlation).23 In a small study by Schuchert et al.28 24 patients with recurrent syncope and negative tilt-table test were enrolled. One patient experienced syncope during monitoring and only 17% (4/24) had syncope during an average of 15 months of follow-up after termination of the monitoring. In one of the earliest reports on the use of ELR, Linzer et al.29 described that arrhythmic ECG documentation (positive or negative) was present in 25% (14/57) of the syncopal events (both pre-syncope and syncope) during 30 days of monitoring in patients with many recurrences. A frequent characteristic of ELR was that a high proportion (up to 50%) of patients failed to wear the device or activate it properly at the time of symptoms. These cited studies varied significantly in the characteristics of patients included and the number of syncope episodes leading up to inclusion in the studies. A Mobile Cardiac Outpatient Telemetry (MCOT) device records ECG continuously and incorporates algorithms for automatic arrhythmia detection and uses wireless (real-time) transmission to a service center. In a randomized study comparing MCOT with traditional ELR Rothman et al.30 found that in a subgroup of patients with syncope, MCOT had a greater diagnostic yield and a shorter time to diagnosis. Further studies are needed to evaluate the efficacy of automatized remote telemetry in the work-up of unexplained syncope. Recently the diagnostic utility of a leadless 14-day ambulatory adhesive patch was described and it seems to have both high patient compliance and feasible arrhythmia detection, although it does not have wireless transmission capabilities. A total of 4029 patients wore the patch in the study, but the initial results did not report specifically for syncope patients and the utility in comparison with ELR and ILR is uncertain at present time.31 The major limitations in the use of ELR are patient compliance, failure to operate the device properly and difficulties handling cutaneous patch electrodes. A costeffectiveness analysis has indicated that the marked improvement in diagnostic yield offsets the cost of the ELR and that they are an economically attractive alternative when compared to Holter monitoring.32 In the Randomized Assessment of Syncope Trial (RAST) Krahn et al.33 randomized 60 patients to a strategy of either “conventional investigation” with an ELR for 2–4 weeks, a electrophysiological testing and a tilt-table test versus a “prolonged monitoring” for 1 year with an ILR. This study suggested that early implantation with ILR was more efficacious (52% diagnosed versus 20%) and more cost-effective than the “conventional” strategy.33 In conclusion the use of ELR is more cost-effective than the Holter but less cost-effective than the ILR as it is limited by the rate of syncopal recurrences. The negative diagnostic (no symptom–ECG correlation) value of the ELR is however very important, they are superior to Holter monitoring as an initial strategy and the role of MCOT and other variants are still to be defined.
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Implantable loop recorders ILRs were developed in the early 1990s and are small (≈60 mm × 20 mm; 15 g) devices that are implanted subcutaneously in the left frontal pectoral region as an outpatient procedure. Currently there are two FDA-approved ILRs available for clinical use. The REVEAL PLUS (Medtronic, Minneapolis, USA) and the CONFIRM (St Jude, St Paul, USA). With improving technology they now have a battery life of approximately 3 years and are able to detect a bipolar ECG signal from small leads on either end of the device. Events can be detected manually or by automatized algorithms and are saved on a solid-state memory up to 40 minutes before and 1–5 minutes after activation. Many observational smaller studies have investigated the use of the ILR with considerable variation. The RAST33 study investigated the use of an ILR compared to a conventional strategy as noted above. In the large multinational Place of Reveal In the Care pathway and Treatment of patients with Unexplained Recurrent Syncope (PICTURE) registry study an ILR-guided diagnosis was demonstrated in 78% of 570 patients with pre-syncope or syncope during an average follow-up of 10 months and 38% (218/570) had documented syncope within this period.34 In patients with recurrent neurally mediated syncope, in contrast to tilt-table testing, the ILR also provides information about the characteristics of the heart rhythm during recurrent syncope35,36 and may help guide decisions regarding specific therapy as previously mentioned.18,35,37 The ISSUE studies gave important understandings of the mechanism and treatment of syncope by the use of ILR. In ISSUE-1, three distinct syncope groups were investigated revealing three novel insights on mechanism: The first group consisted of 35 patients with structural heart disease, reduced ejection fraction and negative electrophysiological study. During a mean follow-up of 6 months, 17% (6/35) patients had recurrence and investigation of the device revealed that (unexpectedly) none of these were due to ventricular tachycardia.13 The second group consisted of 52 patients with bundle branch block and negative electrophysiological study.38 Syncope recurred in 42% (22/52) and most events were due to complete heart block or other block variants. Only 4% in this group had syncope without a significant arrhythmia. In the last group, 111 patients with the absence of structural heart disease and with a normal ECG, had tilt-table tests performed. A total of 34% (38/111) of the patients had recurrence and there was a symptom–ECG correlation in 84% (32/38). Approximately 50% of the patients in this group had one or more prolonged asystolic episodes and the authors concluded that most of these patients had reflex (neutrally mediated) cardioinhibitory syncope. Furthermore there was no good correlation between pre-syncope symptoms and significant arrhythmias recorded by the ILR,12 essentially ruling out pre-syncope as a surrogate marker for arrhythmic true syncope. In the second ISSUE study, ISSUE-2, 392 patients with recurrent suspected neurally mediated syncope were enrolled. During a median follow-up of 9 months, 26% (103/
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392) experienced recurrence. Of these patients 46% (47/103) had asystole during the event and received a pacemaker (PM). This therapeutic intervention with PM reduced the risk of subsequent syncope by 80% when compared to those who did not receive the PM.18 There were concerns however, of a placebo effect of PM implantation.39 In ISSUE-3 which was comparable to ISSUE-2 except for a double-blind approach at time of PM implantation, patients were randomized to pacemaker activated on or off with blinding of patient and physician. A total of 511 patients were implanted with an ILR and dual-chamber permanent pacing was found effective in reducing the relative risk of recurrence of syncope by 57% in patients above the age of 40 years with asystolic neurally mediated syncope. This study supports both early implantation of ILR and subsequent invasive treatment for the otherwise usually benign neurally mediated syncope.40 However, even in this selected asystolic patient category treated with a PM a significant proportion (25%) of the patients continued to faint and the number needed to treat may still be relatively high. The role of the ILR-guided treatment in relatively high-risk patients (bifascicular block, preserved ejection fraction and syncope in patients above the age of 80 years) is currently being examined in the Syncope: Pacing or Recording in ThE Later Years (SPRITELY) study.41 The diagnostic yield of the ILR is indisputable higher than both Holter and ELR due to prolonged monitoring period. In pooled data comprising 506 patients the symptom–ECG correlation was shown in 35% (176/501), only 33% of these were negative diagnostic (symptoms without arrhythmias).11-13,38 In highly selected patients the symptom–ECG correlation was as high as 88%42 and the diagnostic value increased with increasing observation time. Furukawa et al.43 found estimated cumulative diagnostic rates of 30%, 43%, 52%, and 80% at 1, 2, 3, and 4 years of ILR observation time.
Where the ILR is in the work-up? Current European Society of Cardiology guidelines recommend ILR implantation at an early stage in patients with unexplained syncope without high-risk criteria based on efficacy, safety and cost–utility (class I, level A).11,44 This is in line with the above cited limited diagnostic utility of shortterm ECG monitoring.45 An ILR also yields valuable and therapeutic information in unexplained syncope in high-risk patients in whom otherwise comprehensive evaluations have not revealed the cause (class I, level B). Further in older (above 50 years) patients with possible frequent neutrally mediated syncope ILR may be indicated to guide pacemaker therapy for selected asystolic and bradycardic events (class IIA, level B). Lastly ILR also seems plausible for patients when the diagnosis of syncope has not yet been established in selected elderly patients with a history of falls or patients with depression and unexplained loss of consciousness46,47 (class 2B, level C). ILRs should not be used in low-risk patients, unless they have a clear diagnostic or therapeutic purpose. The disadvantages of ILR include the need for a minor surgical procedure, the difficulty of not always being able to differentiate supraventricular from ventricular arrhythmias,
the presence of under- or over-sensing that may exhaust the memory of the ILR, and the initial cost of the device.
ECG diagnosis In summary, a diagnosis can be made if there is a correlation between syncope or pre-syncope and a detected arrhythmia. In the absence of symptom–ECG correlation, ventricular pauses ≥3 s or periods of Mobitz type II atrioventricular block, third-degree atrioventricular block or ventricular tachycardia are arrhythmias that lead to a very plausible cause of the initial syncope as well as a specific treatment. In the absence of an arrhythmia at the time of syncope (but no presyncope), ECG monitoring may exclude arrhythmias as the cause of syncope. Guidelines have adapted the ISSUE classification and definition of rhythm disturbances recorded with the ILR at the time of syncope.11,48
Asymptomatic arrhythmias found during ECG monitoring Asymptomatic arrhythmias are often clinically relevant in decision making for arrhythmia diagnosis and treatment. Auto-activation and detection of arrhythmias aid the clinician, but also provide grounds for questions. Holter, MCOT and ILR monitoring suggests that asymptomatic arrhythmias are quite common in elderly patients with or without syncope and in patients with or without cardiac disease.49-53 It is reasonable to assume that patients with an arrhythmic cause of syncope will also have episodes that do not meet the above-mentioned arrhythmic thresholds to cause symptoms. Detection of asymptomatic marked bradycardia or tachycardia, however, often influences clinician decisions to treat these findings to prevent recurrent syncope, most likely resulting in excessive treatment.
Summary This review explores the evidence and roles of short-term (Holter and ELR) and long-term (ILR) ECG monitoring. After proper risk stratification, in low- or intermediate-risk patients short-term Holter monitoring is reserved for the very few patients in whom syncope is expected to recur within a week, while external loop recorders can be used when syncope is expected to recur within 1 month. In patients, where an arrhythmic cause is suspected but the likelihood of recurrence is low, early use of an implantable loop recorder is recommended and might become the reference standard. The investigations performed in syncope are based on a clinical probability analysis, and the choice of diagnostic testing is predicated upon the results of the initial tests. Therefore the indications and use of ECG monitoring in the work-up of unexplained syncope, in particular, continue to be a debatable subject. A thoughtful and targeted approach with mechanismspecific treatment and guideline-adherent strategy reduces
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health care costs and improves the selection of patients for optimal treatment possibilities.
Statement of Conflict of Interest
15.
16.
M.H.R. has no conflict of interest to disclose. W.Z. has received grants from Boston. 17. REFERENCES
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