Variability of cardioinhibition in vasovagal syncope: differences between subgroups during cardioinhibition and beyond.

PURPOSE: We compared hemodynamic parameters between subjects with marked, intermediate and minimal cardioinhibition during vasovagal syncope. METHODS: The study included subjects with a decrease in heart rate while experiencing a complete vasovagal syncope during tilt-table testing. The subjects were classified as having marked, intermediate or minimal cardioinhibition, based on tertile values of the decrease in heart rate. Hemodynamic parameters between these groups were compared before tilt in the supine position, shortly after tilt and during cardioinhibition. RESULTS: A total of 149 subjects with a median age of 43 (interquartile range 24-60) years were included in the study. Among the three groups with different levels of cardioinhibition, the highest heart rate was observed in subjects with marked cardioinhibition both before and shortly after tilt and at the start of cardioinhibition. The heart rate decrease in these subjects was both larger and faster compared to subjects with minimal and intermediate cardioinhibition. CONCLUSION: Subjects with marked cardioinhibition have both a larger and faster decrease in heart rate compared to subjects with intermediate and minimal cardioinhibition, as early as from the start of cardioinhibition. Marked cardioinhibition is related to differences in hemodynamic profiles already present well before the start of cardioinhibition.

Novel Methods for Quantification of Vasodepression and Cardioinhibition During Tilt-Induced Vasovagal Syncope.

RATIONALE: Assessing the relative contributions of cardioinhibition and vasodepression to the blood pressure (BP) decrease in tilt-induced vasovagal syncope requires methods that reflect BP physiology accurately. OBJECTIVE: To assess the relative contributions of cardioinhibition and vasodepression to tilt-induced vasovagal syncope using novel methods. METHODS AND RESULTS: We studied the parameters determining BP, that is, stroke volume (SV), heart rate (HR), and total peripheral resistance (TPR), in 163 patients with tilt-induced vasovagal syncope documented by continuous ECG and video EEG monitoring. We defined the beginning of cardioinhibition as the start of an HR decrease (HR) before syncope and used logarithms of SV, HR, and TPR ratios to quantify the multiplicative relation BP=SV·HR·TPR. We defined 3 stages before syncope and 2 after it based on direction changes of these parameters. The earliest BP decrease occurred 9 minutes before syncope. Cardioinhibition was observed in 91% of patients at a median time of 58 seconds before syncope. At that time, SV had a strong negative effect on BP, TPR a lesser negative effect, while HR had increased (all P<0.001). At the onset of cardioinhibition, the median HR was at 98 bpm higher than baseline. Cardioinhibition thus initially only represented a reduction of the corrective HR increase but was nonetheless accompanied by an immediate acceleration of the ongoing BP decrease. At syncope, SV and HR contributed similarly to the BP decrease (P<0.001), while TPR did not affect BP. CONCLUSIONS: The novel methods allowed the relative effects of SV, HR, and TPR on BP to be assessed separately, although all act together. The 2 major factors lowering BP in tilt-induced vasovagal syncope were reduced SV and cardioinhibition. We suggest that the term vasodepression in reflex syncope should not be limited to reduced arterial vasoconstriction, reflected in TPR, but should also encompass venous pooling, reflected in SV.

A novel approach to assess hemorrhagic shock severity using the arterially determined left ventricular isovolumic contraction period.

Recently, the ventilatory variation in pre-ejection period (ΔPEP) was found to be useful in the prediction of fluid-responsiveness of patients in shock. In the present study we investigated the behavior of the ventilation-induced variations in the systolic timing intervals in response to a graded hemorrhage protocol. The timing intervals studied included the ventilatory variation in ventricular electromechanical delay (ΔEMD), isovolumic contraction period (determined from the arterial pressure waveform, ΔAIC), pulse travel time (ΔPTT), and ΔPEP. ΔAIC and ΔPEP were evaluated in the aorta and carotid artery (annotated by subscripts Ao and CA) and were compared with the responses of pulse pressure variation (ΔPPAo) and stroke volume variation (ΔSV). The graded hemorrhage protocol, followed by resuscitation using norepinephrine and autologous blood transfusion, was performed in eight anesthetized Yorkshire X Landrace swine. ΔAICAo, ΔAICCA, ΔPEPAo, ΔPEPCA, ΔPPAo, ΔPPCA, and ΔSV showed significant increases during the graded hemorrhage and significant decreases during the subsequent resuscitation. ΔAICAo, ΔAICCA, ΔPEPAo, and ΔPEPCA all correlated well with ΔPPAo and ΔSV (all r ≥ 0.8, all P < 0.001). ΔEMD and ΔPTT did not significantly change throughout the protocol. In contrast with ΔPEPAo, which was significantly higher than ΔPEPCA (P < 0.01), ΔAICAo was not different from ΔAICCA. In conclusion, ventilation-induced preload variation principally affects the arterially determined isovolumic contraction period (AIC). Moreover, ΔAIC can be determined solely from the arterial pressure waveform, whereas ΔPEP also requires ECG measurement. Importantly, ΔAIC determined from either the carotid or aortic pressure waveform are interchangeable, suggesting that, in contrast with ΔPEP, ΔAIC may be site independent.

Influence of Age on Magnitude and Timing of Vasodepression and Cardioinhibition in Tilt-Induced Vasovagal Syncope.

BACKGROUND: Cardioinhibition may diminish with age, but the changing balance of cardioinhibition and vasodepression with age has not been quantified, leaving the mechanism of vasovagal syncope (VVS) in old age unclear. OBJECTIVES: This study sought to quantify age-related changes of vasodepression and cardioinhibition in tilt-induced VVS. METHODS: We studied 163 cases of tilt-induced VVS, evoked using the Italian protocol with blood pressure, heart rate, and video-electroencephalographic monitoring. Presyncope was excluded. Cardioinhibition was defined as the heart rate decrease before syncope; asystolic pauses (≥3 seconds) were divided into early and late asystole, ie, beginning early enough to or too late to be the major cause of loss of consciousness. The log-ratio method was used to quantify contributions of cardioinhibition and vasodepression, assessed in 2 10-second periods before the onset of cardioinhibition and before syncope. RESULTS: With increasing age, cardioinhibition decreased, ie, heart rate decreased less and more slowly near syncope (P < 0.0001), while vasodepression increased. Asystolic pauses were less frequent in the older one-half of the group than the younger one-half (26% vs 57%; P < 0.00001), but when it did, late asystole occurred more often (58% vs 15%; P < 0.001). CONCLUSIONS: The shift toward less cardioinhibition and more vasodepression with increased age probably reflects a physiological shift in circulatory control. The weakening of cardioinhibition with age may detract from the efficacy of pacing in older patients with VVS. Cardioinhibition-vasodepression balance should be considered in pacing decisions in older subjects with VVS.

The onset of ventricular isovolumic contraction as reflected in the carotid artery distension waveform.

The blood pressure waveform carries information about the cardiac contraction and the impedance characteristics of the vascular bed. Here, we demonstrate that the start of isovolumic ventricular contraction is persistently reflected as an inflection point in the pressure wave as recorded in the aortic root (TP(IC)) as well as in the carotid artery distension waveform (TD(IC)) as it travels down the arterial tree. In a group of six patients with normal pressure gradients across the aortic valve after valve replacement, the TP(IC) had a small delay with respect to the onset of isovolumic ventricular contraction (<10 ms). In a group (n = 21) of young presumably healthy volunteers, the inflection point occurred persistently in the carotid distension waveform, as recorded by means of ultrasound, before the systolic foot (intersubject delay between inflection point and systolic foot: mean +/- SD = 40.0 +/- 9.4 ms, intrasubject SD 4.6 ms). Retrograde coronary blood flow during isovolumic ventricular contraction may be the origin of the persistent end-diastolic pressure and distension perturbation. This study shows that the duration of the isovolumic contraction can be reliably extracted from the carotid artery distension waveform.

A modified device for continuous non-invasive blood pressure measurements in humans under hyperbaric and/or oxygen-enriched conditions.

BACKGROUND: It would be desirable to safely and continuously measure blood pressure noninvasively under hyperbaric and/or hyperoxic conditions, in order to explore haemodynamic responses in humans under these conditions. METHODS: A systematic analysis according to 'failure mode and effects analysis' principles of a commercially available beat-by-beat non-invasive blood pressure monitoring device was performed using specifications provided by the manufacturer. Possible failure modes related to pressure resistance and fire hazard in hyperbaric and oxygen-enriched environments were identified and the device modified accordingly to mitigate these risks. The modified device was compared to an unaltered device in five healthy volunteers under normobaric conditions. Measurements were then performed under hyperbaric conditions (243 kPa) in five healthy subjects. RESULTS: Modifications required included: 1) replacement of the carbon brush motorized pump by pressurized air connected through a balanced pressure valve; 2) modification of the 12V power supply connection in the multiplace hyperbaric chamber, and 3) replacement of gas-filled electrolytic capacitors by solid equivalents. There was concurrence between measurements under normobaric conditions, with no significant differences in blood pressure. Measurements under pressure were achieved without problems and matched intermittent measurement of brachial arterial pressure. CONCLUSION: The modified system provides safe, stable, continuous non-invasive blood pressure trends under both normobaric and hyperbaric conditions.

Initiation of ventricular contraction as reflected in the aortic pressure waveform.

Prior to aortic valve opening, aortic pressure is perturbed by ventricular contraction. The onset of this pressure perturbation coincides with the onset of the left ventricular (LV) isovolumic contraction, and hence will be referred to as the start of the arterially detected isovolumic contraction (AIC(start)). In the present study we test the hypothesis that the pressure perturbation indeed has a cardiac origin. In ten Yorkshire-Landrace swine, waveform intensity analysis demonstrated that AIC(start) was followed by a positive intensity wave (0.3 × 10(5) ± 0.3 × 10(5) W (m(2) s(2))(-1)). Timing analysis of LV and aortic pressure waveform showed that AIC(start) was preceded by a LV pressure perturbation (3.8 ± 1.8 ms, p < 0.001). These novel cardiac timing and aortic wave intensity findings reveal the cardiac origin of the pressure perturbation. In 15 Yorkshire-Landrace swine, myocardial motion analysis showed a significantly higher rate of segment shortening during the first part of the LV pressure perturbation. Therefore, both the LV and aortic pressure perturbation are most likely caused by the early phase of myocardial contraction, which also causes mitral valve closure. Consequently, AIC(start) is useful in the determination of the isovolumic contraction period, a well-known marker to quantify cardiac dysfunction.

Coronary-aortic interaction during ventricular isovolumic contraction.

In earlier work, we suggested that the start of the isovolumic contraction period could be detected in arterial pressure waveforms as the start of a temporary pre-systolic pressure perturbation (AIC(start), start of the Arterially detected Isovolumic Contraction), and proposed the retrograde coronary blood volume flow in combination with a backwards traveling pressure wave as its most likely origin. In this study, we tested this hypothesis by means of a coronary artery occlusion protocol. In six Yorkshire × Landrace swine, we simultaneously occluded the left anterior descending (LAD) and left circumflex (LCx) artery for 5 s followed by a 20-s reperfusion period and repeated this sequence at least two more times. A similar procedure was used to occlude only the right coronary artery (RCA) and finally all three main coronary arteries simultaneously. None of the occlusion protocols caused a decrease in the arterial pressure perturbation in the aorta during occlusion (P > 0.20) nor an increase during reactive hyperemia (P > 0.22), despite a higher deceleration of coronary blood volume flow (P = 0.03) or increased coronary conductance (P = 0.04) during hyperemia. These results show that the pre-systolic aortic pressure perturbation does not originate from the coronary arteries.

Quantitative analysis of exercise-induced enhancement of early- and late-systolic retrograde coronary blood flow.

Coronary blood flow (CBF) is reduced and transiently reversed during systole via cardiac contraction. Cardiac contractility, coronary tone, and arterial pressure each influence systolic CBF (CBF(SYS)), particularly by modulating the retrograde component of CBF(SYS). The effect of concurrent changes in these factors on CBF(SYS) during dynamic exercise has not been examined. Using chronically instrumented swine, we hypothesized that dynamic exercise enhances retrograde CBF(SYS). Phasic CBF was examined at rest and during treadmill exercise [2-5 miles/h (mph)]. Absolute values of mean CBF over the cardiac cycle (CBF(CYCLE)) as well as mean CBF in diastole (CBF(DIAS)) and mean CBF(SYS) were increased by exercise, while relative CBF(DIAS) and CBF(SYS) expressed as percentage of mean CBF(CYCLE) were principally unchanged. Early retrograde CBF(SYS) was present at rest and increased in magnitude (-33 +/- 4 ml/min) and as a percent of CBF(CYCLE) (-0.6 +/- 0.1%) at 5 mph. This reversal was transient, comprising 3.7 +/- 0.3% of cardiac cycle duration at 5 mph. Our results also reveal that moderately intense exercise (>3 mph) induced a second CBF reversal in late systole before aortic valve closure. At 5 mph, late retrograde CBF(SYS) amounted to -53 +/- 11 ml/min (-3.1 +/- 0.7% of CBF(CYCLE)) while occupying 11.1 +/- 0.3% of cardiac cycle duration. Wave-intensity analysis revealed that the second flow reversal coincided with an enhanced aortic forward-going decompression wave (vs. rest). Therefore, our data demonstrate a predictable increase in early-systolic CBF reversal during exercise and additionally that exercise induces a late-systolic CBF reversal related to the hemodynamic effects of left ventricular relaxation that is not predictable using current models of phasic CBF.