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Michele Brignole - One of the best experts on this subject based on the ideXlab platform.

  • Plasma adenosine and Neurally Mediated Syncope: ready for clinical use
    EP-Europace, 2020
    Co-Authors: Michele Brignole, Andrea Ungar, Antonella Groppelli, Roberto Brambilla, Gianluca Caldara, Erminio Torresani, Gianfranco Parati, Diana Solari, Martina Rafanelli, Jean-claude Deharo
    Abstract:

    Either central or peripheral baroreceptor reflex abnormalities and/or alterations in neurohumoral mechanisms play a pivotal role in the genesis of Neurally Mediated Syncope. Thus, improving our knowledge of the biochemical mechanisms underlying specific forms of Neurally Mediated Syncope (more properly termed 'neurohumoral Syncope') might allow the development of new therapies that are effective in this specific subgroup. A low-adenosine phenotype of neurohumoral Syncope has recently been identified. Patients who suffer Syncope without prodromes and have a normal heart display a purinergic profile which is the opposite of that observed in vasovagal Syncope patients and is characterized by very low-adenosine plasma level values, low expression of A2A receptors and the predominance of the TC variant in the single nucleotide c.1364 C>T polymorphism of the A2A receptor gene. The typical mechanism of Syncope is an idiopathic paroxysmal atrioventricular block or sinus bradycardia, most often followed by sinus arrest. Since patients with low plasma adenosine levels are highly susceptible to endogenous adenosine, chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, is expected to prevent syncopal recurrences. This hypothesis is supported by results from series of cases and from observational controlled studies.

  • the benefit of pacemaker therapy in patients with Neurally Mediated Syncope and documented asystole a meta analysis of implantable loop recorder studies
    Europace, 2018
    Co-Authors: Michele Brignole, Marco Tomaino, Angel Moya, Jean-claude Deharo, Richard Sutton, Carlo Menozzi, Andrea Ungar
    Abstract:

    Aim: Although the efficacy of cardiac pacing in patients with Neurally Mediated Syncope (NMS) and documented asystole is established, a more robust point estimate of the benefit, which is not possible with any individual study, is lacking. Methods and results: We undertook a meta-analysis of individual participant data from four studies that reported follow-up data on Syncope recurrence with cardiac pacing in patients with NMS who had had an electrocardiographic (ECG) documentation of an asystolic event by means of implantable loop recorder (ILR). Of a total of 1046 patients, who had ILR implanted, 383 (36.6%) patients had an ECG documentation of a diagnostic event during mean follow-up of 13 ± 10 months. Of these, 201 (52%) patients, corresponding to 19.2% of the total ILRs, had an asystolic event of 12.8 ± 11.0 s duration documented and met the criteria for pacemaker therapy. Follow-up was available in 121 (60%) of those patients with asystolic events. Syncope recurred after pacing in 18 (14.9%) patients with an actuarial rate of 13% [95% confidence interval (CI) ±6] at 1 year, 21% (95%CI ±10) at 2 years, and 24% (95%CI ±11) at 3 years. On multivariable Cox regression analysis, positive tilt test response was the only significant predictor of Syncope recurrence with a hazard ratio (95% CI) of 4.3 (1.4-13). On the contrary, type of asystolic event (sinus arrest or atrioventricular block), prodrome, cardiac abnormalities, number and duration of history of Syncope, age, and gender were not predictors of recurrence of Syncope. Conclusion: A long asystolic pause, suitable for pacemaker therapy, was found in one of five patients with ILR. After pacemaker implantation, most of these patients remained free of Syncope recurrence for up to 3 years. The benefit of pacemaker was greater in patients with negative tilt test.

  • benefit of pacemaker therapy in patients with presumed Neurally Mediated Syncope and documented asystole is greater when tilt test is negative an analysis from the third international study on Syncope of uncertain etiology issue 3
    Circulation-arrhythmia and Electrophysiology, 2014
    Co-Authors: Michele Brignole, Marco Tomaino, Angel Moya, Jean-claude Deharo, Matteo Iori, Xulio Beiras, Paolo Donateo, Riccardo Massa, Teresa Kus, Silvia Giuli
    Abstract:

    Background— In the Third International Study on Syncope of Uncertain Etiology (ISSUE-3), cardiac pacing was effective in reducing recurrence of Syncope in patients with presumed Neurally Mediated Syncope (NMS) and documented asystole but Syncope still recurred in 25% of them at 2 years. We have investigated the role of tilt testing (TT) in predicting recurrences. Methods and Results— In 136 patients enrolled in the ISSUE-3, TT was positive in 76 and negative in 60. An asystolic response predicted a similar asystolic form during implantable loop recorder monitoring, with a positive predictive value of 86%. The corresponding values were 48% in patients with non–asystolic TT and 58% in patients with negative TT ( P =0.001 versus asystolic TT). Fifty-two patients (26 TT+ and 26 TT–) with asystolic Neurally Mediated Syncope received a pacemaker. Syncope recurred in 8 TT+ and in 1 TT– patients. At 21 months, the estimated product-limit Syncope recurrence rates were 55% and 5%, respectively ( P =0.004). The TT+ recurrence rate was similar to that seen in 45 untreated patients (control group), which was 64% ( P =0.75). The recurrence rate was similar between 14 patients with asystolic and 12 with non–asystolic responses during TT ( P =0.53). Conclusions— Cardiac pacing was effective in Neurally Mediated Syncope patients with documented asystolic episodes in whom TT was negative; conversely, there was insufficient evidence of efficacy from this data set in patients with a positive TT even when spontaneous asystole was documented. Present observations are unexpected and need to be confirmed by other studies. Clinical Trial Registration— URL: . Unique identifier: [NCT01463358][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01463358&atom=%2Fcircae%2F7%2F1%2F10.atom

  • pacing for Neurally Mediated Syncope how to decide
    Cardiology Journal, 2014
    Co-Authors: Michele Brignole
    Abstract:

    Neurally-Mediated Syncope has a broad clinical spectrum which ranges from typical vasovagal Syncope on one hand, to those situations in which reflex Syncope occurs with uncertain, or even apparently absent, triggers or prodromes, on the other hand. Overlap of clinical features is frequent in clinical practice and makes any classification difficult to apply when selecting patients for cardiac pacing. Typically, the reflex is both hypotensive and cardio-inhibitory. The rationale for efficacy of cardiac pacing is that the cardio-inhibitory reflex is dominant, since there is no role for pacing in preventing vasodilatation and hypotension. Establishing a relationship between symptoms and cardio-inhibitory reflex should be the goal of the clinical evaluation before embarking on permanent pacing. Similar efficacy has been observed in patients affected by dominant cardio-inhibitory reflex irrespective of the clinical form. In general, cardiac pacing should be considered last choice applied only in highly selected patients, i.e. those ≥ 40 years of age, affected by severe forms of reflex Syncope with recurrences associated with frequent injury, often due to the lack of prodromes. Recurrence of Syncope may still occur despite cardiac pacing in a minority of patients.

  • 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
    Co-Authors: Michele Brignole, Dietrich Andresen, Wouter Wieling, Angel Moya, Jean-claude Deharo, Carlo Menozzi, Andrew D. Krahn, Jean Jacques Blanc, Xulio Beiras, Vitantonio Russo
    Abstract:

    Background—The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with Neurally Mediated Syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic Neurally Mediated Syncope. Methods and Results—Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of Syncope with ≥3 s asystole or ≥6 s asystole without Syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was Syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned t...

David G. Benditt - One of the best experts on this subject based on the ideXlab platform.

  • reproducibility of electrocardiographic findings in patients with suspected reflex Neurally Mediated Syncope
    American Journal of Cardiology, 2008
    Co-Authors: Angel Moya, Dietrich Andresen, Wouter Wieling, Roberto Garciacivera, David G. Benditt, Michele Brignole, Richard Sutton, Carlo Menozzi, Jesus F Garciasacristan, Xulio Beiras
    Abstract:

    The reproducibility of electrocardiographic (ECG) recordings in syncopal recurrences and the diagnostic role of nonsyncopal arrhythmias are not well known. The objective of this study was to analyse the reproducibility of the ECG findings recorded with implantable loop recorders in 41 patients with suspected Neurally-Mediated Syncope who were included in the International Study on Syncope of Uncertain Origin-2 study and that had ≥2 events recorded by implantable loop recorders. In these patients, the electrocardiogram obtained with the first documented Syncope (index Syncope) was compared with other recorded events. Twenty-two patients had ≥2 Syncopes, and their electrocardiograms were reproducible in 21 (95%): 15 with sinus rhythm, 5 with asystole, and 1 with ventricular tachycardia; 1 had asystole at first Syncope and sinus rhythm at recurrent Syncope. In 32 patients with nonsyncopal episodes, an arrhythmia was documented in 9, and all of them had the same arrhythmia during the index Syncope (100% reproducibility); conversely, when sinus rhythm was documented (23 patients) during nonsyncopal episodes, an arrhythmia was still documented in 6 during the index Syncope (70% reproducibility; p = 0.0004). In conclusion, the ECG findings during the first Syncope are highly reproducible in subsequent Syncopes. The presence of an arrhythmia during nonsyncopal episodes is also highly predictive of the mechanism of Syncope, but the presence of sinus rhythm does not rule out the possibility of arrhythmia during Syncope. Therefore the finding of an arrhythmia during a nonsyncopal episode allows the etiologic diagnosis of Syncope, and eventually to anticipate treatment, without waiting for Syncope.

  • analysis of rhythm variation during spontaneous cardioinhibitory Neurally Mediated Syncope implications for rdr pacing optimization an issue 2 substudy
    Europace, 2007
    Co-Authors: Michele Brignole, Wouter Wieling, Richard Sutton, Nicoletta Grovale, M K Erickson, Toby Markowitz, Fabrizio Ammirati, David G. Benditt
    Abstract:

    Background Little is known of the variations of the heart rate during spontaneous cardioinhibitory Neurally-Mediated Syncope. Their knowledge has both academic and practical implications for the optimization of rate drop response (RDR) pacing mode. Methods and results We describe variations of the rhythm occurring during 48 syncopal episodes documented by implantable loop recorder. The presyncopal phase of 18 s (interquartile range 9–65) was characterized by a fall in heart rate from 83 ± 20 bpm to maximal bradycardia or (multiple) asystolic pauses which lasted a median of 19 s (10–30). The recovery phase lasted 22 s (7–52). The total duration of the cardioinhibitory reflex was 85 s (47–116). We then calculated the potential increase in benefit that an optimally programmed drop rate detection could provide compared with a reference Lower Rate detection. Compared with Lower Rate detection (defined as two consecutive beats at 40 bpm), drop rate detection (assumed to be drop size = 20 bpm, detection window = 1 min, and drop rate = 50 bpm) would have been able to introduce intervention pacing, a median of 5.7 s (interquartile range −5.1– −10.4) earlier in 28 cases (58%). Conclusion Cardioinhibitory Neurally-Mediated reflex varies widely from a few seconds to some minutes. In our data the total duration was <2 min. Optimal RDR programming, being potentially able to anticipate the detection of the cardioinhibitory reflex by a few seconds, could provide an increase in benefit for cardiac pacing therapy in prevention of Syncope.

  • lack of correlation between the responses to tilt testing and adenosine triphosphate test and the mechanism of spontaneous Neurally Mediated Syncope
    European Heart Journal, 2006
    Co-Authors: Michele Brignole, Dietrich Andresen, Wouter Wieling, Angel Moya, Roberto Garciacivera, David G. Benditt, Richard Sutton, Carlo Menozzi, Nicoletta Grovale, Tiziana De Santo
    Abstract:

    Aims We prospectively correlated the results of tilt testing (TT) and adenosine triphosphate test (ATP) with the findings observed during a spontaneous syncopal relapse by means of an implantable loop recorder (ILR) in patients with a clinical diagnosis of Neurally Mediated Syncope. Methods and results We included patients with three or more clinically severe syncopal episodes in the last 2 years without significant electrocardiographic and cardiac abnormalities. Patients with orthostatic hypotension and carotid sinus Syncope were excluded. After ILR implantation, patients were followed until the first documented Syncope. Among 392 enrolled patients, 343 underwent TT, which was positive in 164 (48%), and 180 ATP test, which was positive in 53 (29%). Syncope was documented by ILR in 106 (26%) patients after a median of 3 months. Patients with positive and negative TT had similar baseline characteristics, syncopal recurrence rate, and mechanism of Syncope, but those with positive TT had more frequently no or slight rhythm variations during spontaneous Syncope (45 vs. 21%, P ¼ 0.02). An asystolic pause was more frequently found during spontaneous Syncope than during TT (45 vs. 21%, P ¼ 0.02), but there was a trend for those with an asystolic response during TT also to have an asystolic response during spontaneous Syncope (75 vs. 37%, P ¼ 0.1). Patients with positive ATP test responses showed syncopal recurrence rates and mechanism of Syncope similar to those with negative ATP tests. Conclusion In patients with Neurally Mediated Syncope, clinical characteristics, outcome, and mechanism of Syncope are poorly correlated and not predicted by the results of TT and ATP test. Therefore, these tests are of little or no value in guiding specific therapy.

  • early application of an implantable loop recorder allows effective specific therapy in patients with recurrent suspected Neurally Mediated Syncope
    European Heart Journal, 2006
    Co-Authors: Michele Brignole, Dietrich Andresen, Wouter Wieling, Angel Moya, Roberto Garciacivera, David G. Benditt, Richard Sutton, Carlo Menozzi, Panos E. Vardas
    Abstract:

    AIMS: This prospective multicentre observational study assessed the efficacy of specific therapy based on implantable loop recorder (ILR) diagnostic observations in patients with recurrent suspected Neurally Mediated Syncope (NMS). METHODS AND RESULTS: Patients with three or more clinically severe syncopal episodes in the last 2 years without significant electrocardiographic and cardiac abnormalities were included. Orthostatic hypotension and carotid sinus Syncope were excluded. After ILR implantation, patients were followed until the first documented Syncope (Phase I). The ILR documentation of this episode determined the subsequent therapy and commenced Phase II follow-up. Among 392 patients, the 1-year recurrence rate of Syncope during Phase I was 33%. One hundred and three patients had a documented episode and entered Phase II: 53 patients received specific therapy [47 a pacemaker because of asystole of a median 11.5 s duration and six anti-tachyarrhythmia therapy (catheter ablation: four, implantable defibrillator: one, anti-arrhythmic drug: one)] and the remaining 50 patients did not receive specific therapy. The 1-year recurrence rate in 53 patients assigned to a specific therapy was 10% (burden 0.07 +/- 0.2 episodes per patient/year) compared with 41% (burden 0.83 +/- 1.57 episodes per patient/year) in the patients without specific therapy (80% relative risk reduction for patients, P = 0.002, and 92% for burden, P = 0.002). The 1-year recurrence rate in patients with pacemakers was 5% (burden 0.05 +/- 0.15 episodes per patient/year). Severe trauma secondary to Syncope relapse occurred in 2% and mild trauma in 4% of the patients. CONCLUSION: A strategy based on early diagnostic ILR application, with therapy delayed until documentation of Syncope allows a safe, specific, and effective therapy in patients with NMS.

  • international study on Syncope of uncertain etiology 2 the management of patients with suspected or certain Neurally Mediated Syncope after the initial evaluation rationale and study design
    Europace : European pacing arrhythmias and cardiac electrophysiology, 2003
    Co-Authors: Michele Brignole, Dietrich Andresen, Wouter Wieling, Angel Moya, Roberto Garciacivera, David G. Benditt, Richard Sutton, Carlo Menozzi, Panos E. Vardas, Roberta Migliorini
    Abstract:

    Study design Multi-centre, prospective observational study Objectives Main objective is to verify the value of implantable loop recorder (ILR) in assessing the mechanism of Syncope and the efficacy of the ILR-guided therapy after Syncope recurrence. Inclusion criteria Patients who met the following criteria are included: suspected or definite Neurally Mediated Syncope based on initial evaluation; greater than or equal to3 Syncope episodes in the last 2 years; severe clinical presentation of Syncope requiring treatment initiation in the judgement of the investigator and age >30 years. Exclusion criteria Patients with one or more of the following are excluded: carotid sinus syndrome; suspected or definite heart disease and high likelihood of cardiac Syncope; symptomatic orthostatic hypotension diagnosed by standing blood pressure measurement; loss of consciousness different from Syncope (e.g. epilepsy, psychiatric, metabolic, drop-attack, TIA, intoxication, cataplexy) and subclavian steal syndrome. End-points The primary end-points are the ECG-documented syncopal events and the Syncope recurrences after application of ILR-guided therapy. Sample size and duration A minimum of 400 patients will be enrolled during an anticipated period of 3 years. (C) 2003 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved

Angel Moya - One of the best experts on this subject based on the ideXlab platform.

  • the benefit of pacemaker therapy in patients with Neurally Mediated Syncope and documented asystole a meta analysis of implantable loop recorder studies
    Europace, 2018
    Co-Authors: Michele Brignole, Marco Tomaino, Angel Moya, Jean-claude Deharo, Richard Sutton, Carlo Menozzi, Andrea Ungar
    Abstract:

    Aim: Although the efficacy of cardiac pacing in patients with Neurally Mediated Syncope (NMS) and documented asystole is established, a more robust point estimate of the benefit, which is not possible with any individual study, is lacking. Methods and results: We undertook a meta-analysis of individual participant data from four studies that reported follow-up data on Syncope recurrence with cardiac pacing in patients with NMS who had had an electrocardiographic (ECG) documentation of an asystolic event by means of implantable loop recorder (ILR). Of a total of 1046 patients, who had ILR implanted, 383 (36.6%) patients had an ECG documentation of a diagnostic event during mean follow-up of 13 ± 10 months. Of these, 201 (52%) patients, corresponding to 19.2% of the total ILRs, had an asystolic event of 12.8 ± 11.0 s duration documented and met the criteria for pacemaker therapy. Follow-up was available in 121 (60%) of those patients with asystolic events. Syncope recurred after pacing in 18 (14.9%) patients with an actuarial rate of 13% [95% confidence interval (CI) ±6] at 1 year, 21% (95%CI ±10) at 2 years, and 24% (95%CI ±11) at 3 years. On multivariable Cox regression analysis, positive tilt test response was the only significant predictor of Syncope recurrence with a hazard ratio (95% CI) of 4.3 (1.4-13). On the contrary, type of asystolic event (sinus arrest or atrioventricular block), prodrome, cardiac abnormalities, number and duration of history of Syncope, age, and gender were not predictors of recurrence of Syncope. Conclusion: A long asystolic pause, suitable for pacemaker therapy, was found in one of five patients with ILR. After pacemaker implantation, most of these patients remained free of Syncope recurrence for up to 3 years. The benefit of pacemaker was greater in patients with negative tilt test.

  • benefit of pacemaker therapy in patients with presumed Neurally Mediated Syncope and documented asystole is greater when tilt test is negative an analysis from the third international study on Syncope of uncertain etiology issue 3
    Circulation-arrhythmia and Electrophysiology, 2014
    Co-Authors: Michele Brignole, Marco Tomaino, Angel Moya, Jean-claude Deharo, Matteo Iori, Xulio Beiras, Paolo Donateo, Riccardo Massa, Teresa Kus, Silvia Giuli
    Abstract:

    Background— In the Third International Study on Syncope of Uncertain Etiology (ISSUE-3), cardiac pacing was effective in reducing recurrence of Syncope in patients with presumed Neurally Mediated Syncope (NMS) and documented asystole but Syncope still recurred in 25% of them at 2 years. We have investigated the role of tilt testing (TT) in predicting recurrences. Methods and Results— In 136 patients enrolled in the ISSUE-3, TT was positive in 76 and negative in 60. An asystolic response predicted a similar asystolic form during implantable loop recorder monitoring, with a positive predictive value of 86%. The corresponding values were 48% in patients with non–asystolic TT and 58% in patients with negative TT ( P =0.001 versus asystolic TT). Fifty-two patients (26 TT+ and 26 TT–) with asystolic Neurally Mediated Syncope received a pacemaker. Syncope recurred in 8 TT+ and in 1 TT– patients. At 21 months, the estimated product-limit Syncope recurrence rates were 55% and 5%, respectively ( P =0.004). The TT+ recurrence rate was similar to that seen in 45 untreated patients (control group), which was 64% ( P =0.75). The recurrence rate was similar between 14 patients with asystolic and 12 with non–asystolic responses during TT ( P =0.53). Conclusions— Cardiac pacing was effective in Neurally Mediated Syncope patients with documented asystolic episodes in whom TT was negative; conversely, there was insufficient evidence of efficacy from this data set in patients with a positive TT even when spontaneous asystole was documented. Present observations are unexpected and need to be confirmed by other studies. Clinical Trial Registration— URL: . Unique identifier: [NCT01463358][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01463358&atom=%2Fcircae%2F7%2F1%2F10.atom

  • 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
    Co-Authors: Michele Brignole, Dietrich Andresen, Wouter Wieling, Angel Moya, Jean-claude Deharo, Carlo Menozzi, Andrew D. Krahn, Jean Jacques Blanc, Xulio Beiras, Vitantonio Russo
    Abstract:

    Background—The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with Neurally Mediated Syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic Neurally Mediated Syncope. Methods and Results—Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of Syncope with ≥3 s asystole or ≥6 s asystole without Syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was Syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned t...

  • tilt testing and Neurally Mediated Syncope too many protocols for one condition or specific protocols for different situations
    European Heart Journal, 2009
    Co-Authors: Angel Moya
    Abstract:

    Syncope, defined as a transient loss of consciousness due to transient global cerebral hypoperfusion, characterized by rapid onset, short duration, and spontaneous complete recovery, is a frequent symptom and can be attributed to different causes.1 The most common aetiology of Syncope is a Neurally Mediated reflex that consists of a transient failure of the cardiovascular mechanisms that normally control haemodynamic stability. This reflex is usually triggered by different stimuli (afferent pathways), leading to sudden withdrawal of sympathetic activity and to an increase in parasympathetic nerve tone (efferent pathways), causing vasodilatation, with consequent hypotension, and bradycardia. The clinical presentation of Neurally Mediated Syncope is not usually uniform; however, it may manifest with different patterns. In some patients, it is initiated by clear adrenergic stimuli such as fear, pain, emotional distress, or medical instrumentation, whereas in others it develops after prolonged orthostatism, hypovolaemia, or carotid sinus stimuli. There are also many patients in whom reflex Syncope develops without any apparent recognizable trigger. On the other hand, some patients complain of typical vegetative prodrome, whereas others develop sudden Syncope without any warning symptom. In addition, although both mechanisms, hypotension and bradycardia, are, by definition, always present, the predominance of one or the other leads to the characteristic patterns of vasodepressor, mixed, or cardioinhibitory reflex Syncope.2 Although all these situations share a common underlying mechanism, i.e. hypotension and bradycardia triggered by some afferent stimuli, these differences have a great impact on the diagnostic process and in therapeutic decisions. Whereas a syncopal episode in a young patient, with clear triggers and prodrome, is easy to diagnose and manage, sudden episodes, without recognizable triggers, particularly … *Corresponding author. Tel: +34 932746166, Fax: +34 932746002, Email: 11193amm{at}comb.es; amoya{at}comb.es

  • reproducibility of electrocardiographic findings in patients with suspected reflex Neurally Mediated Syncope
    American Journal of Cardiology, 2008
    Co-Authors: Angel Moya, Dietrich Andresen, Wouter Wieling, Roberto Garciacivera, David G. Benditt, Michele Brignole, Richard Sutton, Carlo Menozzi, Jesus F Garciasacristan, Xulio Beiras
    Abstract:

    The reproducibility of electrocardiographic (ECG) recordings in syncopal recurrences and the diagnostic role of nonsyncopal arrhythmias are not well known. The objective of this study was to analyse the reproducibility of the ECG findings recorded with implantable loop recorders in 41 patients with suspected Neurally-Mediated Syncope who were included in the International Study on Syncope of Uncertain Origin-2 study and that had ≥2 events recorded by implantable loop recorders. In these patients, the electrocardiogram obtained with the first documented Syncope (index Syncope) was compared with other recorded events. Twenty-two patients had ≥2 Syncopes, and their electrocardiograms were reproducible in 21 (95%): 15 with sinus rhythm, 5 with asystole, and 1 with ventricular tachycardia; 1 had asystole at first Syncope and sinus rhythm at recurrent Syncope. In 32 patients with nonsyncopal episodes, an arrhythmia was documented in 9, and all of them had the same arrhythmia during the index Syncope (100% reproducibility); conversely, when sinus rhythm was documented (23 patients) during nonsyncopal episodes, an arrhythmia was still documented in 6 during the index Syncope (70% reproducibility; p = 0.0004). In conclusion, the ECG findings during the first Syncope are highly reproducible in subsequent Syncopes. The presence of an arrhythmia during nonsyncopal episodes is also highly predictive of the mechanism of Syncope, but the presence of sinus rhythm does not rule out the possibility of arrhythmia during Syncope. Therefore the finding of an arrhythmia during a nonsyncopal episode allows the etiologic diagnosis of Syncope, and eventually to anticipate treatment, without waiting for Syncope.

Keith G Lurie - One of the best experts on this subject based on the ideXlab platform.

  • pharmacotherapy of Neurally Mediated Syncope
    Circulation, 1999
    Co-Authors: David G. Benditt, Gerard J Fahy, Keith G Lurie, Scott Sakaguchi, William H Fabian, Nemer Samniah
    Abstract:

    A wide variety of pharmacological agents are currently used for prevention of recurrent Neurally Mediated Syncope, especially the vasovagal faint. None, however, have unequivocally proven long-term effectiveness based on adequate randomized clinical trials. At the present time, beta-adrenergic receptor blockade, along with agents that increase central volume (eg, fludrocortisone, electrolyte-containing beverages), appear to be favored treatment options. The antiarrhythmic agent disopyramide and various serotonin reuptake blockers have also been reported to be beneficial. Finally, vasoconstrictor agents such as midodrine offer promise and remain the subject of clinical study. Ultimately, though, detailed study of the pathophysiology of these syncopal disorders and more aggressive pursuit of carefully designed placebo-controlled treatment studies are essential if pharmacological prevention of recurrent Neurally Mediated Syncope is to be placed on a firm foundation.

  • Neurally Mediated Syncope
    Current Treatment Options in Cardiovascular Medicine, 1999
    Co-Authors: William H Fabian, David G. Benditt, Keith G Lurie
    Abstract:

    Syncope is a common problem in medical practice. Of the various types of Syncope, the Neurally Mediated syncopal syndromes (of which vasovagal Syncope is the most common) predominate. In most cases, Neurally Mediated Syncope is a solitary event that can be managed with only reassurance, but certain patients (those with multiple recurrences or those who have been injured as a result of Syncope) need further investigation and therapy. Dietary and lifestyle changes are crucial and often overlooked aspects of therapy that may be sufficient to control symptoms. Pharmacologic therapy, which usually starts with beta-blockers or fludrocortisone, can also be effective. Finally, certain patients may continue to have recurrences despite the use of both nonpharmacologic and pharmacologic therapy. It was recently demonstrated that permanent pacing may be effective in preventing recurrent syncopal episodes in some of these patients.

  • characterization of subcutaneous microvascular blood flow during tilt table induced Neurally Mediated Syncope
    Journal of the American College of Cardiology, 1995
    Co-Authors: David G. Benditt, Meng Yang Chen, Ronnell Hansen, Jeffrey Buetikofer, Keith G Lurie
    Abstract:

    Abstract Objectives. This study aimed to characterize subcutaneous blood flow changes during Neurally Mediated Syncope and to determine whether microvasculature oscillation (vasomotion) is characteristically altered in conjunction with syncopal events. Background. Marked pallor is commonly associated with Neurally Mediated Syncope. However, little attention has been paid to the evaluation of subcutaneous blood flow and vasomotion in this setting. Methods. This study utilized laser Doppler flowmetry to assess changes in subcutaneous microvascular blood flow during head-up tilt table testing in 13 patients with Syncope and 6 control subjects. Blood flow and vasomotion frequency were measured continuously before, during and after completion of 80° head-up tilt testing (≤25-min duration). Results. Among the 13 patients with Syncope, tilt testing reproduced syncopal symptoms in 9 (tilt-positive group) but not in 4 (tilt-negative group). None of the six control subjects developed symptoms during testing. Baseline mean subcutaneous blood flow did not differ significantly among the three groups. However, during upright tilt, blood flow gradually diminished in the tilt-positive group, reaching a nadir of 0.8 ± 0.33 ml/min per 100 g of tissue (mean ± SD), but remained relatively constant in the tilt-negative group and control subjects. The difference in mean blood flow response to tilt was statistically significant when the tilt-positive group was compared with either the tilt-negative group or control subjects (p Conclusions. These findings document an expected diminution of subcutaneous blood flow in association with Neurally Mediated Syncope and indicate that characteristic changes in microvasculature oscillation frequency occur in conjunction with syncopal symptoms. To the extent that microvasculature vasomotion is influenced by neural control, the changes in vasomotion frequency are consistent with relative diminution of peripheral sympathetic neural influence during Neurally Mediated syncopal episodes.

  • characterization of subcutaneous microvascular blood flow during tilt table induced Neurally Mediated Syncope
    Journal of the American College of Cardiology, 1995
    Co-Authors: David G. Benditt, Meng Yang Chen, Ronnell Hansen, Jeffrey Buetikofer, Keith G Lurie
    Abstract:

    Objectives. This study aimed to characterize subcutaneous blood flow changes during Neurally Mediated Syncope and to determine whether microvasculature oscillation (vasomotion) is characteristically altered in conjunction with syncopal events. Background. Marked pallor is commonly associated with Neurally Mediated Syncope. However, little attention has been paid to the evaluation of subcutaneous blood flow and vasomotion in this setting. Methods. This study utilized laser Doppler flowmetry to assess changes in subcutaneous microvascular blood flow during head-up tilt table testing in 13 patients with Syncope and 6 control subjects. Blood flow and vasomotion frequency were measured continuously before, during and after completion of 80° head-up tilt testing (≤25-min duration). Results. Among the 13 patients with Syncope, tilt testing reproduced syncopal symptoms in 9 (tilt-positive group) but not in 4 (tilt-negative group). None of the six control subjects developed symptoms during testing. Baseline mean subcutaneous blood flow did not differ significantly among the three groups. However, during upright tilt, blood flow gradually diminished in the tilt-positive group, reaching a nadir of 0.8 ± 0.33 ml/min per 100 g of tissue (mean ± SD), but remained relatively constant in the tilt-negative group and control subjects. The difference in mean blood flow response to tilt was statistically significant when the tilt-positive group was compared with either the tilt-negative group or control subjects (p < 0.001). Similarly, baseline blood flow oscillation frequency did not differ significantly in the three subgroups (tilt-positive group 0.2 ± 0.11 Hz; tilt-negative group 0.2 ± 0.02 Hz; control subjects 0.2 ± 0.11 Hz). Subsequently, during tilt testing only the tilt-positive group exhibited increased oscillation frequency; oscillation frequency remained essentially constant throughout the tilt test in the tilt-negative group and control subjects (p < 0.001, tilt-positive group vs. either the tilt-negative group or control subjects). Conclusions. These findings document an expected diminution of subcutaneous blood flow in association with Neurally Mediated Syncope and indicate that characteristic changes in microvasculature oscillation frequency occur in conjunction with syncopal symptoms. To the extent that microvasculature vasomotion is influenced by neural control, the changes in vasomotion frequency are consistent with relative diminution of peripheral sympathetic neural influence during Neurally Mediated syncopal episodes.

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  • the benefit of pacemaker therapy in patients with Neurally Mediated Syncope and documented asystole a meta analysis of implantable loop recorder studies
    Europace, 2018
    Co-Authors: Michele Brignole, Marco Tomaino, Angel Moya, Jean-claude Deharo, Richard Sutton, Carlo Menozzi, Andrea Ungar
    Abstract:

    Aim: Although the efficacy of cardiac pacing in patients with Neurally Mediated Syncope (NMS) and documented asystole is established, a more robust point estimate of the benefit, which is not possible with any individual study, is lacking. Methods and results: We undertook a meta-analysis of individual participant data from four studies that reported follow-up data on Syncope recurrence with cardiac pacing in patients with NMS who had had an electrocardiographic (ECG) documentation of an asystolic event by means of implantable loop recorder (ILR). Of a total of 1046 patients, who had ILR implanted, 383 (36.6%) patients had an ECG documentation of a diagnostic event during mean follow-up of 13 ± 10 months. Of these, 201 (52%) patients, corresponding to 19.2% of the total ILRs, had an asystolic event of 12.8 ± 11.0 s duration documented and met the criteria for pacemaker therapy. Follow-up was available in 121 (60%) of those patients with asystolic events. Syncope recurred after pacing in 18 (14.9%) patients with an actuarial rate of 13% [95% confidence interval (CI) ±6] at 1 year, 21% (95%CI ±10) at 2 years, and 24% (95%CI ±11) at 3 years. On multivariable Cox regression analysis, positive tilt test response was the only significant predictor of Syncope recurrence with a hazard ratio (95% CI) of 4.3 (1.4-13). On the contrary, type of asystolic event (sinus arrest or atrioventricular block), prodrome, cardiac abnormalities, number and duration of history of Syncope, age, and gender were not predictors of recurrence of Syncope. Conclusion: A long asystolic pause, suitable for pacemaker therapy, was found in one of five patients with ILR. After pacemaker implantation, most of these patients remained free of Syncope recurrence for up to 3 years. The benefit of pacemaker was greater in patients with negative tilt test.

  • 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
    Co-Authors: Michele Brignole, Dietrich Andresen, Wouter Wieling, Angel Moya, Jean-claude Deharo, Carlo Menozzi, Andrew D. Krahn, Jean Jacques Blanc, Xulio Beiras, Vitantonio Russo
    Abstract:

    Background—The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with Neurally Mediated Syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic Neurally Mediated Syncope. Methods and Results—Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of Syncope with ≥3 s asystole or ≥6 s asystole without Syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was Syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned t...

  • reproducibility of electrocardiographic findings in patients with suspected reflex Neurally Mediated Syncope
    American Journal of Cardiology, 2008
    Co-Authors: Angel Moya, Dietrich Andresen, Wouter Wieling, Roberto Garciacivera, David G. Benditt, Michele Brignole, Richard Sutton, Carlo Menozzi, Jesus F Garciasacristan, Xulio Beiras
    Abstract:

    The reproducibility of electrocardiographic (ECG) recordings in syncopal recurrences and the diagnostic role of nonsyncopal arrhythmias are not well known. The objective of this study was to analyse the reproducibility of the ECG findings recorded with implantable loop recorders in 41 patients with suspected Neurally-Mediated Syncope who were included in the International Study on Syncope of Uncertain Origin-2 study and that had ≥2 events recorded by implantable loop recorders. In these patients, the electrocardiogram obtained with the first documented Syncope (index Syncope) was compared with other recorded events. Twenty-two patients had ≥2 Syncopes, and their electrocardiograms were reproducible in 21 (95%): 15 with sinus rhythm, 5 with asystole, and 1 with ventricular tachycardia; 1 had asystole at first Syncope and sinus rhythm at recurrent Syncope. In 32 patients with nonsyncopal episodes, an arrhythmia was documented in 9, and all of them had the same arrhythmia during the index Syncope (100% reproducibility); conversely, when sinus rhythm was documented (23 patients) during nonsyncopal episodes, an arrhythmia was still documented in 6 during the index Syncope (70% reproducibility; p = 0.0004). In conclusion, the ECG findings during the first Syncope are highly reproducible in subsequent Syncopes. The presence of an arrhythmia during nonsyncopal episodes is also highly predictive of the mechanism of Syncope, but the presence of sinus rhythm does not rule out the possibility of arrhythmia during Syncope. Therefore the finding of an arrhythmia during a nonsyncopal episode allows the etiologic diagnosis of Syncope, and eventually to anticipate treatment, without waiting for Syncope.

  • cardioinhibitory carotid sinus hypersensitivity predicts an asystolic mechanism of spontaneous Neurally Mediated Syncope
    Europace, 2007
    Co-Authors: Roberto Maggi, Angel Moya, Michele Brignole, Richard Sutton, Carlo Menozzi, Cristian Podoleanu, Matteo Iori, Franco Giada, Serafino Orazi, Nicoletta Grovale
    Abstract:

    Aims We correlated the finding of cardioinhibitory carotid sinus hypersensitivity (CSH) with that observed during a spontaneous syncopal relapse by means of an implantable loop recorder (ILR). Methods and results We included 18 consecutive patients with suspected recurrent Neurally Mediated Syncope and positive cardioinhibitory response during carotid sinus massage (max pause 5.5+ 1.6 s) who had subsequent documentation of a spontaneous Syncope by means of an ILR. They were compared with a 2:1 age- and sex-matched group of 36 patients with a clinical diagnosis of recurrent Neurally Mediated Syncope and negative response to carotid sinus massage, tilt testing and ATP test. Asystole .3 s was observed at the time of the spontaneous Syncope in 16 (89%) of CSH patients and in 18 (50%) of the control group (P ¼ 0.007). Sinus arrest was the most frequent finding among CSH patients but not among controls (72 vs. 28%, P ¼ 0.003). After ILR documentation, 14 CSH patients with asystole received dual-chamber pacemaker implantation; during 35 + 22 months of follow-up, 2 syncopal episodes recurred in 2 patients (14%), and pre-Syncope occurred in another 2 patients (14%). Syncope burden decreased from 1.68 (95% confidence interval 1.66 2 1.70) episodes per patient per year before to 0.04 (0.038–0.042) after pacemaker implant (98% relative risk reduction). Conclusions In patients with suspected Neurally Mediated Syncope, the finding of cardioinhibitory CSH predicts an asystolic mechanism at the time of spontaneous Syncope and, consequently, suggests a possible benefit of cardiac pacing therapy.

  • lack of correlation between the responses to tilt testing and adenosine triphosphate test and the mechanism of spontaneous Neurally Mediated Syncope
    European Heart Journal, 2006
    Co-Authors: Michele Brignole, Dietrich Andresen, Wouter Wieling, Angel Moya, Roberto Garciacivera, David G. Benditt, Richard Sutton, Carlo Menozzi, Nicoletta Grovale, Tiziana De Santo
    Abstract:

    Aims We prospectively correlated the results of tilt testing (TT) and adenosine triphosphate test (ATP) with the findings observed during a spontaneous syncopal relapse by means of an implantable loop recorder (ILR) in patients with a clinical diagnosis of Neurally Mediated Syncope. Methods and results We included patients with three or more clinically severe syncopal episodes in the last 2 years without significant electrocardiographic and cardiac abnormalities. Patients with orthostatic hypotension and carotid sinus Syncope were excluded. After ILR implantation, patients were followed until the first documented Syncope. Among 392 enrolled patients, 343 underwent TT, which was positive in 164 (48%), and 180 ATP test, which was positive in 53 (29%). Syncope was documented by ILR in 106 (26%) patients after a median of 3 months. Patients with positive and negative TT had similar baseline characteristics, syncopal recurrence rate, and mechanism of Syncope, but those with positive TT had more frequently no or slight rhythm variations during spontaneous Syncope (45 vs. 21%, P ¼ 0.02). An asystolic pause was more frequently found during spontaneous Syncope than during TT (45 vs. 21%, P ¼ 0.02), but there was a trend for those with an asystolic response during TT also to have an asystolic response during spontaneous Syncope (75 vs. 37%, P ¼ 0.1). Patients with positive ATP test responses showed syncopal recurrence rates and mechanism of Syncope similar to those with negative ATP tests. Conclusion In patients with Neurally Mediated Syncope, clinical characteristics, outcome, and mechanism of Syncope are poorly correlated and not predicted by the results of TT and ATP test. Therefore, these tests are of little or no value in guiding specific therapy.