Cardiovascular regulation in the period preceding vasovagal syncope in conscious humans

Abstract

To study cardiovascular control in the period leading to vasovagal syncope we monitored beat-to-beat blood pressure, heart rate (HR) and forearm blood flow in 14 patients with posturally related syncope, from supine through to tilt-induced pre-syncope. Signals of arterial blood pressure (BP) from a Finapres photoplethysmograph and an electrocardiograph (ECG) were fed into a NeuroScope system for continuous analysis. Non-invasive indices of cardiac vagal tone (CVT) and cardiac sensitivity to baroreflex (CSB) were derived on a beat-to-beat basis from these data. Brachial vascular resistance (VR) was assessed intermittently from brachial blood flow velocity (Doppler ultrasound) divided by mean arterial pressure (MAP). Patients underwent a progressive orthostatic stress test, which continued to pre-syncope and consisted of 20 min head-up tilt (HUT) at 60 deg, 10 min combined HUT and lower body suction (LBNP) at -20 mmHg followed by LBNP at -40 mmHg. Pre-syncope was defined as a fall in BP to below 80 mmHg systolic accompanied by symptoms. Baseline supine values were: MAP (means +/- S.E.M.) 84.9 +/- 3.2 mmHg; HR, 63.9 +/- 3.2 beats min-1; CVT, 10.8 +/- 2.6 (arbitrary units) and CSB, 8.2 +/- 1.6 ms mmHg-1. HUT alone provoked pre-syncope in 30 % of the patients whilst the remaining 70 % required LBNP. The cardiovascular responses leading to pre-syncope can be described in four phases. Phase 1, full compensation: where VR increased by 70.9 +/- 0.9 %, MAP was 89.2 +/- 3.8 mmHg and HR was 74.8 +/- 3.2 beats min-1 but CVT decreased to 3.5 +/- 0.5 units and CSB to 2.7 +/- 0.4 ms mmHg-1. Phase 2, tachycardia: a progressive increase in heart rate peaking at 104.2 +/- 5.1 beats min-1. Phase 3, instability: characterised by oscillations in BP and also often in HR; CVT and CSB also decreased to their lowest levels. Phase 4, pre-syncope: characterised by sudden decreases in arterial blood pressure and heart rate associated with intensification of the symptoms of pre-syncope. This study has given a clearer picture of the cardiovascular events leading up to pre-syncope. However, the mechanisms behind what causes a fully compensated system suddenly to become unstable remain unknown.

Figures

Figure 1. Analog signal input into the NeuroScope for calculation of cardiovascular variables

Continuous analog signals of blood pressure waveforms from a digital artery obtained by photoplethysmography (upper trace) and electrocardiogram (ECG, lower trace) fed into the NeuroScope system for measurement of arterial BP, the ECG R-R intervals (RR1 and RR2) representing pulse intervals and cardiac sensitivity to baroreflex (CSB). The point of inflexion in the arterial BP trace at DP represents the diastolic pressure and the point of inflexion at SP represents the systolic pressure in the same cardiac cycle. The mean arterial pressure of this cardiac cycle is the arithmetic mean of all pressures starting from DP, through SP and ending at DP1, sampled at 200 Hz. The CSB is the change in pulse intervals per unit change in systolic pressures and is represented by a 10-s-wide moving average of the quantity: (RR2 - RR1)/(SP2 - SP1) measured in ms mmHg−1 (see text for more details).

Figure 5. Segment of a continuous record of cardiovascular variables acquired in real-time during response phase 3 at a progressive orthostatic stress in a representative subject

This is a phase of cardiovascular instability; the important event here is the rhythmic oscillations of vascular pressure (see Table 1 for a list of all important cardiovascular events in this experiment). The arterial blood pressure (BP) trace shows the oscillations of systolic (SBP, upper trace) and diastolic (lower trace) pressures. These were associated with erratic and large variation in heart rate (HR) demonstrating the instability during this phase. The two derived variables, cardiac sensitivity to baroreflex (CSB) and cardiac vagal tone (CVT) measured in arbitrary units of a linear vagal scale (LVS) both dropped to levels lower than the previous phase, but continued to vary up and down. It is notable here that elevations in CSB are associated with reduced amplitudes of oscillations in both BP and HR. The amplitude and period of the oscillations of blood pressure were calculated as the mean of the three maximal fluctuations: amplitude, in mmHg, 1/6[(b−a) + (b−c) + (d−c) + (d−e) + (f−e) + (f−g)]; period, measured in seconds: 1/3 (g−a), where (g − a) is the time difference between points g and a. Time was measured from the beginning of the experiment.

Figure 2. Continuous record of cardiovascular variables during the entire orthostatic stress test in two subjects (A and B) with very different orthostatic tolerances (OT) showing the four response phases (1, 2, 3, and 4) leading to pre-syncope

The start of the tilt is indicated by the vertical dotted line (T). Arterial blood pressure (BP) shows the systolic (upper trace) and diastolic (lower trace) values both displaying clear borders between response phases 3 and 4. Note the elevation of BP just before the start of phase 3 in both subjects; this was characteristic in all subjects studied. Heart rate (HR) responses show clear borders between response phases 1 and 2. Two derived indices, cardiac sensitivity to baroreflex (CSB) and cardiac vagal tone (CVT) measured in arbitrary units of a linear vagal scale (LVS) are also shown. Note that the elevation of BP just before the beginning of response phase 3 coincides with further drops in both CSB and CVT levels to their lowest values during the entire experiment in both subjects, and this occurred in all subjects studied. During phase 1 HR increased, BP was stable, but there were large decreases in CSB and CVT. During phases 2 and 3 CSB and CVT decreased further but phase 4 was associated with sharp increases in these two variables. The subject in A had OT of only 3 min starting from the head-up tilt at T. The subject in B had a good OT of 32 min. This latter subject required lower body negative pressure of −20 mmHg at S1 and −40 mmHg at S2 to overcome the OT.

Figure 3. Continuous record of cardiovascular responses to head-up tilt (at T) during full compensation in the response phase 1 recorded in real-time in a representative subject

The important event in this response phase to orthostatic stress is a stable cardiovascular compensation (grey arrow; see Table 1 for a list of all important cardiovascular events in this experiment). There was an initial dip in arterial blood pressure (BP) that recovered within 30 s to values higher than the pre-tilt period. The upper BP trace is systolic and the lower trace is diastolic pressure. Note that following head-up tilt, both systolic and diastolic pressures were well compensated and remained stable. The heart rate (HR) increased steeply then varied about a mid value close to 80 beats min−1; the pre-tilt mid value was 71 beat min−1. Two derived variables, cardiac sensitivity to baroreflex (CSB) and cardiac vagal tone (CVT) measured in arbitrary units of a linear vagal scale (LVS), both decreased steeply and then varied about mid values that were about 30 % of the pre-tilt period. Time was measured from the beginning of the experiment.

Figure 4. Segment of a continuous record of cardiovascular variables acquired in real-time during response phase 2 at a progressive orthostatic stress in a representative subject

The important events in this phase are a sudden start of tachycardia (vertical dotted line) and a ramp increase of heart rate (HR) to a peak at P (see Table 1 for a list of all important cardiovascular events in this experiment). The arterial blood pressure (BP) trace shows the systolic (upper trace) and diastolic (lower trace) pressures. The abrupt and progressive increase in HR marks the beginning of response phase 2 during orthostatic stress. The amplitude of BP variation increased during this phase and there was a degree of overlap between phases 2 and 3 (see Fig. 5 for definition of response phase 3). The sudden decrease in pulse pressure (measured as the difference between systolic and diastolic pressures) towards the end was seen in all subjects studied. The two derived variables, cardiac sensitivity to baroreflex (CSB) and cardiac vagal tone (CVT) measured in arbitrary units of a linear vagal scale (LVS) gradually decreased towards zero in steps. Time was measured from the beginning of the experiment.

Figure 6. Segment of a continuous record of cardiovascular variables acquired in real-time during response phase 4 (pre-syncope) at a progressive orthostatic stress in a subject who showed a gradual stepwise regulation of the baroreflex response

This is a phase of cardiovascular decompensation and the important events are a sudden start of progressive decrease in arterial blood pressure (BP, vertical broken line) ending in troughs (P1 and P2), and a sudden start of a progressive decrease in heart rate (HR) at (C1) ending in a trough (C2). The two derived variables, cardiac sensitivity to baroreflex (CSB) and cardiac vagal tone (CVT) measured in arbitrary units of a linear vagal scale (LVS), represent brainstem regulation of baroreceptor function. The CSB increased gradually in steps starting from a very low value (B1) to a peak (B2) and CVT also increased gradually starting from a very low value (V1) to a peak (V2), but V1 preceded B1 by 3 s (see Table 1 for a list of all important cardiovascular events in this experiment). In this subject BP decreased over the course of 1 min, following which the orthostatic stress was terminated. During the fall in pressure, HR remained high and CSB and CVT remained low. Following the return to a supine position there was a marked decrease in HR and increases in CSB and CVT. Note that at the beginning of vascular decompensation, the levels of both CVT and CSB were close to or at zero and did not begin to rise until the BP was at its trough. Time was measured from the beginning of the experiment.

Figure 7. Segment of a continuous record of cardiovascular variables acquired in real-time during response phase 4 (pre-syncope) at a progressive orthostatic stress in a subject who showed abrupt baroreflex reaction leading to asystole

The pre-syncope started with simultaneous decreases in arterial blood pressure (BP) and heart rate (HR). The BP traces are systolic (upper) and diastolic (lower) pressures. The asystole at C2 lasted for 3.1 s followed later on by a brief period of second-degree heart blocks at C3. The two derived variables, cardiac sensitivity to baroreflex (CSB) and cardiac vagal tone (CVT) measured in arbitrary units of linear vagal scale (LVS), represent brainstem regulation of baroreceptor function. The CVT increased abruptly from a value close to zero at V1 to about 120 units at V2 preceding and leading directly to asystole. The brief period of heart blocks was also associated with large increases in CVT. The CSB also rose abruptly in large steps from a very low value at B1 to a peak at B2, but V1 preceded B1 by 30 s. The asystole and second-degree heart blocks did not impede recovery from the pre-syncope. It is notable that the level of CVT preceding the asystole was considerably higher than the average supine level of 8.4 units in this subject, or the average of 10.8 ± 2.6 units in all the subjects studied.