Cardiac Electrophysiologic and Hemodynamic Correlates of Neurally Mediated Syncope Meng Yang Chen, MD, Irvin F. Goldenberg, MD, Simon Milstein, MD, Jeffrey Buetikofer, MD, Adrian Almquist, MD, John Lesser, MD, and David G. Benditt, MD This study assessed the temporal relation of RR in- terval, AH interval and systemic blood pressure changes during induced symptomatic bradycardia- hypotension episodes in 14 patients with recurrent syncope suspected of being neurally mediated. Up- right tilt with isoproterenol reproduced symptoms in 9 of 14 patients (positive response) and was neg- ative in 5 of 14 (negative response). lsoproterenol alone shortened supine RR intervals in all patients. With tilt, however, isoproterenol prolonged RR in- tervals in those with positive results (supine 519 f 124 ms vs tilt 845 f 212 ms, p <O.OOS) while fur- ther shortening RR intervals among negative re- sponders (supine 436 f SO ms vs tilt 377 f 82 ms, p <O.OS). Similarly, tilt with isoproterenol pro- longed AH intervals in patients with positive re- sponses despite RR prolongation, while shortening AH in negative responders. Additionally, with com- bined tilt and isoproterenol, systemic arterial pres- sure decreased significantly in patients with posi- tive responses (systolic 99 f 13 vs 57 f 13 mm Hg, p <O.OOl, diastolic 62 f 17 vs 28 f 9 mm Hg, p <O.OOl) but not in patients with negative re- sponses. Further, onset of hypotension (42 f 14 seconds after tilt) preceded onset of RR interval prolongation (52 f 23 seconds after tilt). Syncope (142 f 72 seconds after tilt) coincided closely with nadir of systemic pressure (136 f 74 seconds) and both tended to precede maximum RR prolongation (152 f 87 seconds). Thus, the bradycardia and hy- potension associated with neurally mediated synco- pe exhibit characteristic but distinctly different time courses, with arterial pressure changes devel- oping earlier and coinciding more closely with symptom development. (Am J Cardiol 1989;63:66-72) T ransient loss of consciousness (syncope) occurs commonly in man, often being the result of par- oxysmal bradycardia and hypotensionof neurally mediated origin (e.g., vasovagal syncope, postmicturi- tion syncope).’ However, despite its frequent oc- currence, the sporadic nature of spontaneous neurally mediated bradycardia and hypotension complicatesthe substantiation of the diagnosisand usually precludes the detailed prospectiveassessment of the electrophysiologic and hemodynamic characteristics of the syndrome.Re- cently, application of upright tilt testing techniques in the electrophysiologic laboratory has provided a means of evaluating susceptibility to neurally mediated synco- pe in many individuals. 2m6 Furthermore, preliminary findings indicate that intravenous isoproterenol infusion in conjunction with upright tilt testing may be of addi- tional value in unmasking susceptibility to symptomatic bradycardia and hypotension.2,4,5 This study used the combined upright tilt testing technique with isoproterenol infusion to assess relations among heart rate, atrioventricular (AV) conduction in- tervals and systemicarterial pressure changes during in- duced neurally mediated bradycardia-hypotension epi- sodesin patients with recurrent syncope of previously unexplained origin. Our findings indicate a distinct tem- poral sequence of eventsdiffering from those previously noted in bradycardia-hypotension of carotid sinus syn- drome etiology.4 METHODS Patients: Fourteen patients (5 men and 9 women, ages 18 to 59 years) participated in this study. All pa- tients fulfilled the following criteria: (1) history of at least 3 episodes of presyncope or syncope which re- From the Department of Medicine, University of Minnesota Medical School, and the Minneapolis Heart Institute, Minneapolis, Minnesota. Dr. Chen was supported in part by a grant-in-aid from the Education Ministry, People’s Republic of China, and by the Minnesota Medical Foundation Electrophysiology Research Fund. This work was complet- ed during Dr. Benditt’s tenure as an Established Investigator of the American Heart Association, Dallas, Texas. Dr. Almquist was support- ed in part by the Kenneth N. Rosen Fellowship of the North American Society for Pacing and Electrophysiology (NASPE). Manuscript re- ceived December 15. 1987: revised manuscript received and accepted March 18, 1988. Address for reprints: David G. Benditt, MD, University of Minne- sota Medical School. Box 341 UMHC, Minneapolis, Minnesota 55455. Dr. Chen’s present address: Fujian Provincial Research Institute for Medical Sciences, Wu-Shi Road, Fuzhou, Fujian, People’s Republic of China. Dr. Almquist’s present address: Cardiology Division, Marshfield Clinic, Marshfield, Wisconsin. 66 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 63