Physiological phenomenology of neurally-mediated syncope with management implications

Abstract

Background: Due to lack of efficacy in recent trials, current guidelines for the treatment of neurally-mediated (vasovagal) syncope do not promote cardiac pacemaker implantation. However, the finding of asystole during head-up tilt -induced (pre)syncope may lead to excessive cardioinhibitory syncope diagnosis and treatment with cardiac pacemakers as blood pressure is often discontinuously measured. Furthermore, physicians may be more inclined to implant cardiac pacemakers in older patients. We hypothesized that true cardioinhibitory syncope in which the decrease in heart rate precedes the fall in blood pressure is a very rare finding which might explain the lack of efficacy of pacemakers in neurally-mediated syncope.

Methods: We studied 173 consecutive patients referred for unexplained syncope (114 women, 59 men, 42 ± 1 years, 17 ± 2 syncopal episodes). All had experienced (pre)syncope during head-up tilt testing followed by additional lower body negative suction. We classified hemodynamic responses according to the modified Vasovagal Syncope International Study (VASIS) classification as mixed response (VASIS I), cardioinhibitory without (VASIS IIa) or with asystole (VASIS IIb), and vasodepressor (VASIS III). Then, we defined the exact temporal relationship between hypotension and bradycardia to identify patients with true cardioinhibitory syncope.

Results: Of the (pre)syncopal events during tilt testing, 63% were classified as VASIS I, 6% as VASIS IIb, 2% as VASIS IIa, and 29% as VASIS III. Cardioinhibitory responses (VASIS class II) progressively decreased from the youngest to the oldest age quartile. With more detailed temporal analysis, blood pressure reduction preceded the heart-rate decrease in all but six individuals (97%) overall and in 10 out of 11 patients with asystole (VASIS IIb).

Conclusions: Hypotension precedes bradycardia onset during head-up tilt-induced (pre)syncope in the vast majority of patients, even in those classified as cardioinhibitory syncope according to the modified VASIS classification. Furthermore, cardioinhibitory syncope becomes less frequent with increasing age.

Figure 1. Original tracings of blood pressure (upper tracings) and heart rate (lower tracings) in four representative individuals who experienced a cardioinhibitory response with asystole (VASIS class IIb) during head-up tilt.

Black and white arrows indicate the onset of hypotension and bradycardia, respectively. Hypotension preceded the onset of bradycardia in most (Panels A–C) but not all patients (Panel D). Panel A: female, 33 years; panel B: female, 52 years; panel C: female 17 years; panel D: female, 32 years.

Figure 2. Individual data and mean±SEM in the difference between the onset of hypotension and the onset of bradycardia stratified for age quartiles.

Hypotension preceded the decrease in heart rate in all but six individuals (97%) irrespective of age.

Figure 3. Individual data and mean±SEM in the difference between the onset of hypotension and the onset of bradycardia for those patients who experienced asystole during head-up tilt (VASIS class IIb).

Hypotension preceded the decrease in heart rate in all but one individual (91%).

Figure 4. Mean values of heart rate (upper panel) and mean blood pressure (lower panel) at 5 sec intervals in the supine position, during early head-up tilt (HUT), and during tilt-induced (pre)syncope stratified for age (green: 1^st quartile, 12–24 years, n = 26; blue: 2^nd quartile, 25–42 years, n = 27; violet: 3^rd quartile, 43–57 years, n = 36; red: 4^th quartile, 58–79 years, n = 20).

The vertical lines indicate the onset of decreases in heart rate and blood pressure, respectively. Younger patients had a larger increase in heart rate with head-up tilt. However, the onset of hemodynamic events began earlier with increasing age. Furthermore, the decrease in heart rate upon tilt-induced (pre)syncope was progressively blunted with increasing age.

Figure 5. Occurrence of cardioinhibitory responses with asystole (VASIS IIb) for age quartiles.

Asystole became progressively rarer with increasing age (p<.05).