JACC Vol . 22, No. 4 1123 October 1993 :1123-9 Role of Autonomic Reflexes in Syncope Associated With Paroxysmal Atrial Fibrillation MICHELE BRIGNOLE, MD, FESC, LORELLA GIANFRANCHI, MD, CARLO MENOZZI, MD,* ANTONIO RAVIELE, MD,t DANIELE ODDONE, MD, GINO LOLLI, MD,* NICOLA BOTTONI, MD* Lat'agna, Reggio Ernilia anmid Mestre, Italy Objectives, The purpose of this study was to evaluate the role of and in 2 (12%) of 16 control subjects (p = 0.0004) . The Induction autonomic reflexes in the genesis of syncope associated with the of atrial fibrillation in the upright position eligited syncope In 16 onset of paroxysmal atrial fibrillation . (42%) of 38 patients but in none of 16 control subjects (p = 0 .001). Background. Syncope associated with paroxysmal atrial fibril- At The beginning of atrial fibrillation, systolic blood pressure was lation has been Interpreted as an ominous finding predictive of lower in patients than in control subjects (88 t 32 vs . 127 t rapid ventricular rates. However, various mechanisms may be 32 aim Hg), whereas mean heart rate was similar (142 t 35 vs . Involved when heart rate is not particularly high . 134 t 25 beats/mint) . The correlation between heart rate and Methods. Forty patients (age 60 s: 14 years, 21) men, 20 systolic blood pressure was weak (r = 0 .35), and In five patients women) with syncope and atrial fibrillation were compared with syncope occurred at a heart rate !5130 beats/min. At the time of 16 control subjects (age 66 t 13 years, 8 men, 8 women) with syncope, heart rate decreased (-12 t 21 beats/min) in patients atrial fibrillation without syncope. Carotid sinus massage and with induced syncope, whereas it remained unchanged in patients head-up tilt testing (at 60° for 60 min at baseline and during without indu'. -.4 ,scope (+1 ± 17 beats/min, p = 0.04) or slightly isoproterenol infusion) were performed during sinus rhythm . A increased in control subjects (+9 t 21 beats/min, p = 0 .009). positive response was defined as the induction of syncope . Atria] Conclusions . Patients with syncope associated with paroxysmal fibrillation was also induced on a tilt table at 60° by means of short atrial fibrillation are predisposed to an abnormal neural response bursts of atrial pacing. during both sinus rhythm and arrhythmia . In some patients the Results. Results of carotid sinus massage were positive in 15 onset at atrial fibrillation triggers vasovagal syncope . (37%) of 40 patients but in no control subjects (p = 0 .002) . (J Am Coll Cardiol 1993;22 :1123-9) Head-up tilt test findings were positive in 25 (66%) of 38 patients Syncope is an unusual clinical presentation of paroxysmal Nonhemodynamic mechanisms may be even more readly atrial fibrillation, and its cause remains uncertain . It has been suspected when heart rate is not particularly high . It is well claimed that a fast ventricular rate at the onset of atrial known that the onset of paroxysmal tachycardia produces a fibrillation is the main factor responsible for syncope as a hemodynamic disturbance that evokes a compensatory car- consequence of hemodynamic deterioration secondary to diovascular response (2,3) . This response, which is mediated the critical reduction in diastolic filling time . Fast ventricular mainly by reflex changes in autonomic nervous tone, is very rates are common during paroxysmal atrial fibrillation in often effective in restoring both blood pressure and cardiac patients affected by enhanced atrioventricular (AV) conduc- output during tachycardia to levels similar to those existing tion or accessory bypass tract . Nevertheless, Auricchio et before the onset of arrhythmia. Moreover, intense vagal al. (1) did not find any difference in heart rate among patients stimulation can cause atrial fibrillation (4,5), and it has with and without a history of syncope when atrial fibrillation recently been suggested that atrial fibrillation may result was induced during electrophysiologic study . They therefore from vagal stimulation occurring at the time of vasovagal suggested that other factors may play a role in the genesis of syncope (6) . In this study we therefore evaluated the role of the syncope . autonomic reflexes in the genesis of syncope associated with the onset of paroxysmal atrial fibrillation . From the Laboratory of Electrophysiology and Pacing . Service of Cardi- ology, Ospedali Riuniti, Lavagna ; *Laboratory of Elecirophysiology and Methods Pacing, Service of Cardiology, Ospedale SM Nuova. Reggio Emiliu; and . 40 tDepartment of Cardiology, Ospedale Umberto I, Mestre. Italy. Selection of patients. From January 1991 to June 1992 Manuscript received December 8 . 1992; revised manuscript received patients affected by syncope associated with paroxysmal March 26.1993 . accepted March 31, 1993 . atrial fibrillation met the inclusion criteria and were enrolled Address for corresoondence: Michele Brignole. MD, FESC. Via A. Grilli 164,1-16041 Borzonasca (GE), Italy. in the study . They accounted for 6% of the overall popula- 0735.1097!931$6.00 01993 by the American College of Cardiology 1124 BRIGNOLE ET AL . JACC Vol. 22, No . 4 SYNCOPE AT THE ONSET OF ATRIAL FIBRILLATION October 1"3-1123-9 Table 1. Clinical Characteristics of the Study Groups between 8:00 AM and 1:00 PM . All cardioactive and vasoac- Patients Control Subjects tive drugs were withdrawn . Informed consent was obtained (n = 40) (n = 16) from all participants. The method of execution of carotid sinus massage and the head-up tilt test have been previously 60 ± 14 66± 13 Age In) . Male gender 2000) 800) described and validated (7-9) ECO abnormalities Carotid sinus massage was performed on both right and Overall 1600) 7 (44) left carotid sinuses in the supine and erect positions for 10 s . Sinus bradycardia 4 I Vasodepressor reflex was evaluated after atropine infusion Ist degree AV block 2 0 when indicated. A positive response was defined as the wave abnormalities 6 3 ST-T development of syncope in association with bradycardia or Q wave 3 0 hypotension, or both . Bundle branch block 2 4 Bclwcardlographk abnormalities 21(521 7 (44) The baseline head-up tilt test protocol consisted of a 60° Fractional shortening (%) 36 t 10 4018 tilt for 60 min or until the occurrence of syncope . If the test Structural heart disease did not induce syncope, the patient or control subject was Overall 25021 1109) lowered into the supine position for 30 min before under- Atherosclerotic 14 7 going the test during isoproterenol infusion . Previous myocardial infarction 3 0 Head-up tilt testing during isoproterenol infusion con- Valvviw S 4 sisted of a 60° tilt for 10 min repeated in successive stages (at Atrial seplal aneurysm 3 0 5-min intervals) with use of graded isoproterenol infusion t SD or number of subjects . AV Values presented are mean value ('%) rates of I to 5 pg/min. aidoventrkular : ECO . electrocardiographic. The upright induction of atria) fibrillation was attempted on a tilt table at 60° immediately after the upright position had been achieved for a maximum of 3 min . Short-duration tion of 672 patients referred to us for investigation of (<5 s) atrial bursts at rates ranging from 300 to 800 beats/min syncope from the emergency room, inpatient service and were delivered until atria) fibrillation L-30 s in duration was ambulatory program. induced. The duration of tilt before initiation of atrial fibril- To be included in the study, the patients had to fulfill the lation was 64 ± 47 s . When atrial fibrillation was induced, the following criteria: 1) unexpected syncope that was immedi- patient was maintained in the upright position for 2 min . If ately preceded and followed by palpitation; 2) documenta- syncope occurred, the patient was rapidly returned to the tion, within 6 h of the event, of paroxysmal atrial fibrillation supine position . Ducting induction procedures, beat to beat lasting <24 h ; 3) absence of electrocardiographic (ECO) finger arterial pressure was monitored continuously by or electrophysiologic evidence of enhanced AV conduction the Penile: volume-clamp method (10) using a finger cuff or accessory bypass tract ; 4) exclusion of other enuses for (Ohmeda Monitoring System) . The arm was supported with syncope on the basis of a standardized evaluation used in a mobile arm plate to keep the finger at heart level in the our departments that has been previously described (7); upright position. Blood pressure was recorded simulta- 5) absence of severe heart failure (New York Heart Associ- neously with the ECG on a paper recorder. For each patient, ation functional class I or II) and of recent acute illness . mean heart rate and systolic pressure were calculated for the The clinical characteristics of the patients are summa- initial 30 s from the onset of atrial fibrillation or until the dud in Table 1 . Syncope invariably occurred while the occurrence of syncope. Changes in mean finger arterial patient was standing or sitting, at rest or during mild activity. pressure, as measured by the Finapres technique, have been At the first examination after the syncopal attack, atrial shown to match closely changes in arterial pressure mea- fibrillation was well tolerated. No signs of cardiovascular sured by invasive techniques during syncope induced by collapse were detected, and no patient reported symptoms passive tilt testing or during induced tachycardia (11,12) . other than palpitation . The average heart rate was 140 ± The upright position was chosen for the induction of atrial 29 beatslmin, fibrillation for two reasons: 1) because spontaneous syncope COW group. The control group consisted of 16 patients always occurred in the sitting or standing position, and without syncope or presyncope who were affected by par- 2) because previous studies have demonstrated that syncope oxysmal atria) fibrillation (Table 1). The average heart rate due to tachyarrhythmia is more likely to be reproduced during the last episode was 144 ± 22 beatslmin . They were during electrophysiologic study in the upright rather than the recruited during the same period as the syncope group .