The implantable loop recorder (ILR) is a small device manufactured by Medtronic Inc., Minneapolis, MN, which is implanted subcutaneously close to the heart. It has the ability to record the electrical activity of the heart, store rhythm disturbances within set parameters and can be triggered by the patient to store events. The loop recorder is a device with a high diagnostic yield and offers precision in diagnosis to the enlightened specialist.
Indications of the Implantable Loop Recorder
In cases of syncope, a major concern in diagnostic testing is that the symptom is transient and is not a disease. Typically, patients are asymptomatic at the time of evaluation and the opportunity to capture a spontaneous event during testing is rare. As a result, evaluation has focused on the detection of abnormalities that could plausibly cause loss of consciousness. This necessarily leads to uncertainty in establishing the reason for the syncope. No reference standard for most of the tests exists; however, due to the episodic nature of syncope, correlating spontaneous syncopal episodes with an abnormal finding can be considered as a reference standard.
The ILR, a device that has recently been made available, is placed subcutaneously in a patient under local anaesthesia. The monitor has a solid state loop memory and a battery life of 15 to 18 months. The current version stores an electrocardiogram (ECG) that includes tracings recorded up to 40 minutes before and two minutes after activation by the patient. If the patient activates the device when consciousness returns, the probability of demonstrating a correlation between ECG signals and syncope is high. The initial clinical experience was published in 1995 by Krahn et al.1 A multicentre study has evaluated the safety and efficacy of a diagnostic strategy based on ILR in a heterogeneous group of 85 patients with unexplained syncope.2 A symptom ECG correlation was found in 27% of cases and presyncope ECG correlation in 32% of cases. Cardiac rhythm at the time of symptoms was various, thus reflecting the heterogeneity of the enrolled population - 29 patients showed normal sinus rhythm, three patients supraventricular tachyarrhythmia and 18 patients bradyarrhythmias supposed to be neurally mediated in seven cases.
Studies in the Field
The International Study of Syncope of Uncertain Etiology (ISSUE) was a multicentre prospective study aimed at analysing the diagnostic contribution of implantable loop recorders in predefined groups of patients with syncope of uncertain origin. The first, or isolated, syncopal group included patients without structural heart disease or with minor heart abnormalities that were considered to be without clinical relevance and were not suggestive of a cardiac cause of syncope.3 The patients had no intraventricular conduction defects and the complete work-up, including tilt table testing, revealed no abnormalities. The second or tilt-positive group was similar to the first group except that tilt testing induced isolated syncope.3 Patients in the third group, or suspected bradycardia group, had bundle branch block and an abnormal response to electrophysiological testing.4 Patients of the fourth group, or suspected tachycardia group, were patients with overt heart disease at risk of ventricular arrhythmia, as these were patients with previous myocardial infarction (MI) or cardiomyopathy with depressed ejection fraction or non-sustained ventricular tachycardia in whom an electrophysiological study did not induce sustained ventricular arrhythmias.5
Requirements for inclusion in the study were a careful history and physical examination, baseline ECG, carotid sinus massage, ECG and 24-hour ambulatory monitoring - electrophysiological study in the case of heart abnormalities or history of palpitations and any other test necessary to definitively to determine the cause of syncope. When eligibility was established, patients underwent subcutaneous loop recorder implantation. The recommended programmed mode was one syncopal event, 21 minutes of pre-activation tracings and one minute post-activation. Patients were instructed to activate the device after every episode of syncope or presyncope. The primary end-point was the analysis of the ECG tracing obtained during the first syncopal episode, which was correctly recorded by the device.
ILRs were implanted in 111 patients with syncope (mean age 63 ┬▒ 16 years, 56 men), absence of significant structural heart disease and a normal ECG (isolated syncope group and tilt-positive syncope group).3 Tilt testing triggered isolated syncope in 29 patients and none in 82. The patients had experienced three or more episodes of syncope during the previous two years and were followed-up for three to 15 months. Baseline characteristics were similar in both groups. Follow-up results were also similar (see Table 1). Syncope recurred in 28 and 10 patients (34% of each group) respectively and ECG correlation was found in 24 and eight patients respectively.
The most frequent finding - recorded in 46% of isolated syncope patients and 62% of tilt-positive patients - was one or more prolonged asystolic pauses due mainly to sinus arrest, preceded for a few minutes by progressive bradycardia or progressive tachycardiabradycardia. Bradycardia without pauses was observed in 8% and 12% of cases. The remaining patients had normal sinus rhythm or sinus tachycardia except for one who had ectopic atrial tachycardia. In the tilt-positive group asystolic syncope was also recorded when the type of response to tilt testing was vasodepressor or mixed. Presyncopal episodes were never characterised by asystolic pauses - normal sinus rhythm was the most frequent finding. Only one patient (1%) sustained severe injury due to syncopal relapse. The patient belonged to the isolated syncope group and had normal sinus rhythm at the time of the syncopal relapse. No patient died during the study period. At the end of the study, 10 isolated patients and four tilt-positive patients received permanent pacemakers on the basis of the loop recorder findings.
ILRs were implanted in 52 patients (mean age 71 ┬▒ eight years, 43 men) with syncope, bundle branch block and a normal conventional work-up including a complete electrophysiological study (suspected bradycardia group).4 The patients had a median of three episodes of syncope during the previous two years. During a follow-up period of three to 15 months, syncope recurred in 22 patients (42%) after a median of 48 days in 19 of these patients.
The most frequent finding - recorded in 17 patients - was one or more prolonged asystolic pauses mainly due to atrioventricular block (12 cases) or sinus arrest (five cases). The remaining two patients had normal sinus rhythm or sinus tachycardia. The onset of bradycardia was always sudden but sometimes preceded by ventricular premature beats. The median duration of the arrhythmic event was 47 seconds. Three other patients developed non-syncopal persistent third-degree atrioventricular block and two patients had presyncope due to atrioventricular block with asystole; intermittent or stable atrioventricular block was observed in 17 patients (33%). The actuarial estimates of atrioventricular block were 24%, 34% and 34% at three, nine and 15 months (see Table 1).
No baseline clinical variable predicted the development of stable or intermittent atrioventricular block during follow-up but patients with right bundle branch block without axis deviation and those with a history of syncope going back more than two years tended not to develop atrioventricular block. No patients sustained injury due to syncopal relapse. As a result of the study findings, 23 patients (44%) underwent implantation of a permanent pacemaker. No therapy was given to the other patients.
Finally, an ILR was applied in 35 patients with overt heart disease at risk of ventricular arrhythmia, as these were patients with previous MI or cardiomyopathy with depressed ejection fraction or non-sustained ventricular tachycardia in whom an electrophysiological study was unremarkable (suspected tachycardia group).5 During a follow-up of three to 15 months, syncope recurred in six patients (17%) after a mean of six ┬▒ five months - in three patients the mechanism of syncope was bradycardia with long pauses (sudden onset atrioventricular block in two cases and sinus arrest in one case). In one patient there was stable sinus tachycardia and in two patients who had chronic atrial fibrillation there was an increase in ventricular rate. A total of 23 episodes of presyncope was documented in eight patients (23%), no rhythm variation or mild tachycardia in 12 cases, paroxysmal atrial fibrillation or atrial tachycardia in 10 cases and sustained ventricular tachycardia in one case (see Table 1). During the study period no patients died or suffered from injury due to syncopal relapse. At the end of the study a permanent pacemaker was implanted in three patients and an implantable defibrillator was inserted in one patient. Anti-arrhythmic drugs were given to four patients and an anti-epileptic drug in one patient.
Summary and Conclusions
Several important results arose from the authorÔÇÖs study. The patients with isolated unexplained syncope and those with an abnormal response to tilt testing had similar clinical characteristics and outcome - that is, a low recurrence rate for at least one year and a low risk of injury and adverse events. This finding suggests that the two groups may have been part of the same population.2 Among the patients in both groups who had a documented recurrence, the most frequent finding was bradycardia at the time of the episode. Typically, these patients had progressive sinus bradycardia, most often followed by ventricular asystole due to sinus arrest or progressive tachycardia followed by progressive bradycardia and ventricular asystole due to sinus arrest. Very long asystolic pauses were recorded at the time of syncope in most cases.
These findings strongly suggest that, in both groups, syncope was probably neurally mediated and that the most frequent mechanism was a dominant cardioinhibitory reflex with prolonged asystolic pauses. The finding that syncope is mostly associated with long asystolic pauses has never been stressed before. This result could be regarded as typical of those forms of neurally mediated syncope characterised by advanced age and a specific clinical presentation without warning.
In the tilt-positive patients, asystolic syncope was also recorded despite a vasodepressor or missed response to tilt testing. It therefore seems that spontaneous syncope is much more frequently asystolic than would be expected on the basis of the results of tilt testing, which cannot be used to predict the type of response to the spontaneous attack. This finding confirms those of a small retrospective study and offers an explanation as to why pacemaker therapy is more effective than expected in preventing syncopal recurrences.3,4
In patients with bundle branch block and abnormal electrophysiological findings, most syncopal recurrences have a homogeneous mechanism characterised by prolonged asystolic pauses mainly due to sudden onset of paroxysmal atrioventricular block. These findings are consistent with the clinical feature of Stokes-Adams symptoms; thus, a negative electrophysiological investigation cannot rule out paroxysmal atrioventricular block as the cause of syncope. In the patients with isolated unexplained syncope or tilt-positive syncope, there was also a high incidence of bradycardia-related syncope, but the mechanism was largely different. In these groups, rather than being sudden, the onset of the asystolic pauses was usually preceded by progressive bradycardia or tachycardia and the arrhythmia was sinus arrest instead of atrioventricular block. These varying findings are consistent with different causes - intrinsic disease of the His-Purkinje system in patients with bundle branch block and an abnormal neurally mediated reflex in the other groups.
The patients with unexplained syncope, structural heart disease and negative electrophysiological study had a favourable medium-term outcome with no cases of death and a low recurrence rate of syncope without related injury. The mechanism of syncope was heterogeneous and ventricular tachyarrhythmia was unlikely. Even in patients with overt heart disease, syncope is not necessarily an ominous finding and the outcome largely depends on the clinical features of the patients. It seems that only the inducibility of sustained ventricular tachycardia or a very depressed systolic function can predict a syncope due to ventricular arrhythmia and, conversely, their absence may predict a more favourable outcome.
The ISSUE experience showed that an ILR-guided strategy is safe and efficacious in directing therapy in some frequent subsets of patients with unexplained syncope. ISSUE subgroups may be regarded as some of the indications for ILR implantation.
The benign nature of isolated and tilt-positive syncope, the low recurrence rate and the low risk of related injury observed suggest the strategy of postponing treatment, pacemaker implantation in particular, until a definite diagnosis can be made by documenting a spontaneous syncopal relapse. Due to the fact that presyncope did not prove to be an accurate surrogate for syncope in establishing diagnosis, therapy should not be guided by presyncopal findings. In accordance with this approach, 16 patients (14%) underwent ILR-guided specific therapy immediately after the first syncopal episode was documented.
Even if the most frequent cause of syncope in patients with bundle branch block and abnormal electrophysiogical findings was paroxysmal atrioventricular block, most patients did not experience the block for more than one year and none sustained injury due to syncopal relapse. An ILR-guided strategy therefore seems reasonable, with pacemaker implantation safely delayed until symptomatic bradycardia can be documented. In accordance with this approach, 44% of the authorsÔÇÖ patients received a pacemaker after their first documented episode of syncope.
An important point worth highlighting is that structural heart disease and syncope do not automatically equate to ventricular arrhythmias and high mortality. Patients with structural heart disease, well-preserved left ventricular function and negative electrophysiological study appear to behave more like patients without structural heart disease in the aetiology of syncope and prognosis. An ILR-guided strategy seems reasonable, with specific therapy delayed until a definite diagnosis is made. In accordance with this approach, 11% of the authorsÔÇÖ patients finally received a pacemaker or a defibrillator and another 14% received pharmacological therapy after their first documented syncope.
Overall, it can be stated that the ILR is a powerful diagnostic tool that hitherto has been vastly underused. The authors have calculated that the potential need in the community is nine per million in those under 65 and 110 per million in those over 65 years of age.6 Ôûá
- Krahn A, Klein G, Norris C, Yee R, The etiology of syncope in patients with negative tilt table and electrophysiological testing, Circulation (1995);92: pp. 1,819-1,826.
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- Krahn A D, Klein G J, Yee R, Takle-Newhouse T, Norris C, Use of an extended monitoring strategy in patients with problematic syncope. Reveal investigators, Circulation (1999);26:99: pp. 406-410, 163.
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- Moya A, Brignole M, Menozzi C et al., Mechanism of syncope in patients with isolated syncope and in patients with tilt positive syncope, Circulation (2001);104: pp. 1,261-1,267.
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- Brignole M, Menozzi C, Moya A et al., The mechanism of syncope in patients with bundle branch block and negative electrophysiological test, Circulation (2001);104: pp. 2,045-2,050.
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- Menozzi C, Brignole M, Garcia-Civera R et al., Mechanism of syncope in patients with heart disease and negative electrophysiological test, Circulation (2002);105: pp. 2,741-2,745.
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- Brignole M, Menozzi C, Maggi R et al., The usage and diagnostic yield of the implantable loop recorder in detection of the mechanism of syncope and in guiding effective anti-arrhythmic therapy in older people, Europace (2005);7: in press.