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ORIGINAL ARTICLES |
From the Department of Cardiology, The Hatter Institute and Centre for Cardiology, University College London Hospitals, London, UK (P.T., P.S., C.R.); The London College of Clinical Hypnosis (Medical), London, UK (V.NB., U.J., A.J.); Department of Cardiac and Vascular Sciences, St Georges’ Hospital Medical School, London, UK (K.H., M.M.).
Address correspondence and reprint requests to Dr. Peter Taggart, Department of Cardiology, The Hatter Institute and Centre for Cardiology, University College London Hospitals, Grafton Way, London WC1E 6DB, UK. E-mail: peter.taggart{at}uclh.org
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSNOTESREFERENCES |
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Methods: Twelve healthy volunteers (6 male, age 18–35, mean 25 years) experienced a series of different emotions intended to induce a wide range of autonomic response (42 test epochs) on two separate occasions, with and without hypnosis, with continuous electrocardiogram recording. Low- (LF) and HF (high-frequency) heart rate variability was measured and ventricular repolarization was assessed using the relative T-wave residua (proportion of nondipolar components of the T wave) calculated for the T-onset – T peak (TWR-peak T), T peak –T end (TWR-end T), and the whole T wave (TWR).
Results: Emotionally induced changes in LF and LF/HF ratio correlated with changes in TWR, e.g., (R = 0.51, p < .001; R = 0.59, p < .0001; and R = 0.59, p < .0003, for LF/HF versus TWR, TWR-Peak T, and TWR-end T, respectively. Mental relaxation induced by hypnosis increased LF power (1,205 ms2) versus 624 ms2, p < .003 for hypnotized versus nonhypnotized state), HF power (1,619 ms2 versus 572 ms2), p < .0004), and reduced LF/HF ratio (1.0 versus 1.5, p = .052) and was associated with a marked reduction in the changes in repolarization in response to emotion, e.g., 10.7 x 10–6 versus 5.0 x10–6, p < .03 for TWR.
Conclusions: a) Mental stress in the absence of ischemia altered repolarization inhomogeneity via change in the autonomic balance. b) Mental relaxation induced by hypnosis greatly reduced the effect of mental stress on repolarization. c) These findings may have implications for arrhythmogenesis.
Key Words: mental stress • arrhythmia • electrophysiology • EKG • hypnosis
Abbreviations: EKG = electrocardiogram; LF = low frequency; HF = high frequency; LF/HF = low frequency/high frequency ratio; TWR = T-wave residua.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSNOTESREFERENCES |
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The exact mechanism by which sympathetic activity induced by mental stress triggers or facilitates ventricular arrhythmias in the absence of ischemia is not clear. One possible mechanism is increased heterogeneity of ventricular repolarization, which is an important predisposing factor for ventricular re-entrant arrhythmias (7,8). It is known from studies in animal models that sympathetic stimulation increases heterogeneity of ventricular repolarization (9). It is also known that emotion may alter repolarization parameters that are correlated with repolarization heterogeneity. For example, mental stress enhances T-wave alternans in animals (10) and in humans susceptible to cardiac arrhythmias (11). However, no systematic data in humans are available on the link between autonomic balance in response to emotion and ventricular repolarization.
In the present study, we induced a series of different emotions intended to span a wide range of autonomic responses, i.e., from mainly sympathetic to parasympathetic effects, on ventricular repolarization. The latter was quantified by the nondipolar (i.e., not contained in the main cardiac dipole, or heart vector) components of the electrocardiogram (EKG) T wave, which are only weakly correlated with conventional repolarization parameters such as QT interval and QT dispersion (12,13), and which are increased in various patient groups compared with healthy controls (12) and contain independent prognostic power (14). Autonomic balance was assessed using heart rate variability (HRV). In order to minimize the possibility of inducing myocardial ischemia during mental stress, only young healthy subjects with no apparent heart disease were studied.
To further investigate the autonomic effects of mental stress on ventricular repolarization, all mental stress tests were also investigated under hypnosis, which is known to cause a shift in sympatho-vagal balance toward overall vagal effects (15,16).
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSNOTESREFERENCES |
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Procedure
Each subject attended on two occasions at the same time of day. Two ambulatory EKG recorders were fitted: one for analysis of HRV (Reynolds Medical) and a second for analysis of T-wave repolarization parameters (Marquette SEER-MC). The subjects were rested in the semirecumbent position, and a sequence of emotions was induced. Because different emotions produce diverse sympathetic and parasympathetic effects (17–21), the test protocols were designed to include a range of different emotions intended to generate as wide a range of autonomic responses as possible. Each emotion was either self-induced by recall of real life situations or induced by presenting pictures of emotive scenes. Six subjects (3M, 3F) experienced the emotions of anger, happiness, the recollection of pain, and humor induced by recall. Each emotional epoch lasted 5 minutes separated by 5 minutes rest (Figure 1, protocol 1). The other 6 subjects experienced the emotions of disgust, fear and a combination of fear with disgust (Figure 1, protocol 2). Disgust was induced by presenting pictures depicting unpleasant scenes accompanied by a graphic verbal description. Fear was then induced by recall and maintained through a further presentation of pictures of unpleasant scenes. These three epochs were consecutive, i.e., lasting a total of 15 minutes with no intervening rest periods. Each subject underwent the same test sequence on two occasions on separate days. On one of the two occasions, a hypnotic state was induced by a medical hypnotist before the start of the emotional test sequence. On the occasion when hypnosis was not performed the subject was engaged in light conversation for 10 minutes before the emotional test sequence (Figure 1).
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Hypnosis
Hypnosis was induced by a standard technique (22) using an eye fixation technique whereby the subject is asked to gaze at a spot of their choosing. Direct and authoritarian suggestions for the body to grow heavy, tired, and sleepy were given. Hypnosis was deepened with a 10 to 1 countdown technique, and direct suggestions on hypnotic sleep were made. Communication with subjects under hypnosis was maintained through the installation of an ideo-motor response, an unconsciously controlled finger movement to obtain "yes" or "no" responses. The subjects were then awakened after the last emotional epoch. Autonomic activity has been shown to vary with self-reported estimates of stress (23). Self-rating scores were obtained for the perceived intensity of the emotions experienced during the hypnotized protocol and the nonhypnotized protocol. The order of allocation to hypnosis first or no hypnosis first was alternate for consecutive subjects. Hypnosis and the stress protocols were administered by different people. As far as possible, the intensity of the stress protocols was standardized for the hypnotized and nonhypnotized occasions by the same duration and order of each emotional epoch as interrogation by the same person. The participants were treated identically on the two occasions apart from the induction of hypnosis before the emotional tests and awakening afterward.
EKG Recordings and HRV
EKG was recorded continuously during the whole procedure using two devices: three-channel ambulatory EKG-recorder (Delmar Reynolds Medical Ltd.) for HRV measurements, and 12-lead digital EKG recorder (SEER MC, GE Marquette, Milwaukee, WI) for repolarization measurements (T-wave residua; TWR). HRV and repolarization measurements were analysed by different people both blind to the identity of the subjects and the interventions. R-R intervals for HRV power spectral density analysis were analysed using the Pathfinder 700 system (Delmar Reynolds Medical Ltd.) computed for low frequency band power (LF 0.04–0.15 Hz), high frequency band power (HF 0.15–0.4 Hz) and LF/HF ratio. Values were obtained for LF at 2 minute intervals and for HF at 1 minute intervals (24). No clinically evident changes in respiration occurred.
Analysis of Repolarization
The 12-lead digital recorder was programmed to acquire one 10-second 12-lead EKG every 10 seconds (i.e., continuously). From each lead of each 10-second 12-lead EKG recording the so-called median beat was constructed, which, compared with the native EKG signal, has an improved signal-to-noise ratio (25). Analysis of repolarization was performed on the series of median beats. The nondipolar (i.e., not included in the main cardiac dipole, or heart vector) components of the T wave (T wave residua, TWR) were calculated using a previously reported method, which has been described in detail (12,26). In brief, the method is based on singular value decomposition of the 8 independent leads of the standard 12-lead EKG (any 2 peripheral plus the 6 precordial leads) (12). Using this method, the EKG is reconstructed in another system of 8 independent (i.e., orthogonal leads). In this system, the first lead contains the maximum energy of the EKG single in one direction, the second lead the maximum of the remaining energy in a direction perpendicular to the first, etc. In this way, the energy of the first three orthogonal leads corresponds to the heart vector, whereas the energy of the remaining leads four to eight corresponds to nondipolar components. TWR quantify the proportion of the EKG signal that cannot be explained by a single moving dipole (the heart vector) during repolarization. They are considered to be due to localized dipoles during the recovery phase, which are cancelled when integrated into the overall dipole of the T wave (27). Thus, TWR represent local variations in the action potential shape and duration that are lost when the whole electrical activity of the heart is presented as a single dipole (heart vector) as, for example, in orthogonal XYZ leads and vectorcardiography. Therefore, their quantification is considered to provide a measure of the degree of localized depolarization heterogeneity throughout ventricular myocardium Normally, TWR represent a very small proportion of the whole ECG signal (12,28), and their increase signifies increased depolarization heterogeneity.
TWR were calculated separately for the Tonset –Tpeak (TWR-P), Tpeak –Tend (TWR-E) as well as for the whole T wave (TWR). The reasons for this were that because the nondipolar EKG content is not constant throughout depolarization and repolarization (29), further information may be gained from subdivisions of the T wave. In addition, many arrhythmias develop from a reentrant circuit between endocardium and epicardium, i.e., transmurally. The peak to the end of the T wave is thought to relate electrophysiologically to transmural repolarization (30) and hence provide an indication of increased repolarization inhomogeneity, which predisposes to transmural reentrant arrhythmias
Statistical Analysis
Correlation between the autonomic measures of HRV (low frequency (LF), high frequency (HF), LF/HF ratio) and the three measures of repolarization (TWR, TWR-peak, TWR-end) were made by Pearson correlation coefficient and simple linear regression, e.g., Table 1 and Figures 2 and 3. TWR parameters were assessed as proportion (%) as described (12). Changes in HRV and repolarization from control during the mental stress tasks were assessed using analysis of variance (ANOVA) and Student’s t test as appropriate. A p value of <0.05 was considered significant (Table 2).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSNOTESREFERENCES |
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Correlation Between the Autonomic Response to Emotion and Repolarization
Correlations were computed for the effect of each of the autonomic measures (LF, HF, LF/HF ratio) on each of the three measures of repolarization (TWR, TWR-peak T, TWR-end T). Positive correlations were obtained for the changes in response to emotion of LF power and the LF/HF ratio but not for HF power on all three repolarization parameters. Plots for the LF/HF ratio are shown in Figure 2. The results are similar for all three TWR measures. The results of all computations are given in Table 1.
Effect of Hypnotic Relaxation on the Influence of Emotion on Repolarization
In order to test the hypothesis that relaxation techniques, one of which is self-hypnosis and others which are effectively variation on self-hypnosis, may reduce repolarization changes in response to emotional stress, each subject underwent the same emotional test sequence during hypnotic relaxation. Self-rating scores showed no difference for the perceived intensity of the emotions experienced during hypnosis (6.5 ± 1.7, mean ± SD on a scale of 1 to 10) compared with the nonhypnotized state (7.0 ± 1.2). The hypnotic state (during the control periods) was associated with an increase in LF power (1,205 ms2 versus 624 ms2, p < .003), a larger increase in HF power (1 619 ms2 versus 572 ms2, p < .0004), and a resultant trend toward a lower LF/HF ratio 1.0 versus 1.5 (p = .52). This pattern was maintained throughout the protocols. The repolarization response to the emotional epochs during hypnotic relaxation was markedly reduced compared with the repolarization changes to the same emotional epochs in the unhypnotized state (Figure 3). The correlation between the emotionally induced autonomic response and changes in repolarization (Figure 2) was lost during relaxation (Figure 3, Table 1). Figure 4 presents comparisons between the mean values of increase of the three TWR measures during emotional stress with and without hypnosis.
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Heart Rate
In keeping with the study design, which was intended to induce a diverse range of autonomic responses, the stress protocols resulted in heart rate changes that varied widely. Heart rates increased in 32 (76%) and decreased below control in 10 (24%) of the emotional test epochs in the absence of hypnosis, and increased in 26 (62%) and decreased in 16 (38%) of the tests during hypnosis. These heart rate changes occurred over a range of +19 to –9 beats/minute in the absence of hypnosis and +15 to –5 beats/minute during hypnosis. As a result of some stress periods increasing heart rate and others decreasing heart rate, mean heart rates during control periods and during test periods, respectively, were similar (72.6 ± 10.5 and 75.1 ± 10.4 beats/minute (p ns). During hypnotic relaxation, heart rates were significantly lower: 66.2 ± 9 during control periods (p < .005 versus unhypnotized control) and 68.0 ± 11.7 during the emotional test epochs (p < .006 versus unhypnotized test period).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSNOTESREFERENCES |
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Autonomic Effects of Emotional Stress
As expected, the emotions generated in these studies resulted in a wide range of responses of both LF and HF components. Although mental stress is most commonly associated with increased sympathetic predominance, some emotions have been shown to be associated with considerable parasympathetic activity (17–20). Indeed, there is growing evidence for the specificity of emotions, with different emotions engaging different patterns of autonomic response (21). The interpretation of LF and HF peaks as markers of sympathetic and parasympathetic activity, respectively, is not straightforward. The LF peak has been shown experimentally to be influenced by both sympathetic and parasympathetic activity (31,32). In our studies, the increase in LF and decrease in LF/HF ratio during hypnosis was most likely due to a decrease in sympathetic and increase in parasympathetic activity. This would be in keeping with studies showing a shift in autonomic balance toward the parasympathetic during hypnosis (15,16). However, our study was not intended to compare the effects of different emotions but to generate a sufficiently diverse autonomic response to facilitate assessment of the relationship of these responses with effects on repolarization.
Autonomic Effects on Ventricular Repolarization
A number of possibilities underlie the mechanism by which emotion may influence repolarization homogeneity in the myocardium in the absence of ischemia through the intermediary of altered autonomic activity. Animal studies have shown that sympathetic stimulation causes a temporary non–steady state during which action potentials shorten nonhomogeneously, thereby creating dispersion of repolarization (9). Therefore, the speed of the intervention and the rate of adaptation are likely to be important in some situations. This is evident from a study in which overt EKG T-wave changes were induced in response to abrupt awakening by an alarm call (33). However, these adaptive responses are relatively short lived and unlikely to be relevant to the present study. Regional differences in receptor density and regional differences in neural traffic to the heart are alternative possibilities. Several animal studies have created increased dispersion of repolarization or refractoriness by stimulation of sympathetic nerves, which shortens action potential duration selectively in the regions supplied by the stimulated nerves (34,35). The right and left cardiac sympathetic nerves are asymmetrically distributed on the ventricles (36). Therefore, one possible mechanism for diverse repolarization changes in response to different mental stimuli would be that central brain processing might result in asymmetrical distribution of neural traffic to the heart. Such a possibility, although speculative, receives support from recent increasing evidence for regional cortical representation of different emotions (37), and different cardiovascular responses when emotion engages different cortical areas (38).
Mental Relaxation
The mechanism underlying the striking reduction in the effect of emotion on repolarization inhomogeneity during hypnotic relaxation is at present unclear. The hypnotic state has been shown to exert both central and peripheral effects, affecting both cortical and brainstem regions (16) as well as being associated with a shift of autonomic balance toward overall parasympathetic effects (15). Reduction in arousal would seem a less likely explanation because there was no significant difference in the self-rating scores for the nonhypnotized and hypnotized emotions. In our studies, the LF/HF ratio was shifted toward the HF, in line with observations of others (16). One possibility, therefore, is that the shift toward parasympathetic dominance during hypnosis may exert an effect on repolarization inhomogeneity that is opposite to the effect of sympathetic stimulation on repolarization seen experimentally (9). An alternative possibility, albeit speculative, is that the central effects of hypnosis (16) may have altered the central processing of the emotional tasks and resulted in an altered distribution of neural traffic to the heart.
Similar results were obtained with all three TWR measures of repolarization heterogeneity. As mentioned earlier, the subdivisions of the T wave, i.e., T onset to the peak of the T wave and peak T to end of the T wave, were included because of temporal variation of the nondipolar components during the T wave as well as different physiological implications of different parts of the T wave. The overall similarity that we observed in all three TWR measures suggests that the effects of the mental stress protocols were uniform both temporally during the T wave and spatially in the heart.
Methodological Considerations
Several aspects of methodology require mention. The study was performed in young healthy subjects. Although the main population at risk from ventricular arrhythmias are patients with coronary artery disease (39) and mental stress is well known to induce ischemia in some of these patients (2–5), a large proportion of sudden presumed arrhythmic deaths occur in the absence of demonstrable ischemia (39). Furthermore, mental stress has been shown to facilitate the induction of ventricular arrhythmia during electrophysiological testing in these patients in the absence of ischemia (6). These findings strongly suggest a nonischemic as well as an ischemic component. In order to identify such a nonischemic component, we studied young healthy subjects in whom mental stress–induced ischemia would seem highly unlikely. We did not anticipate arrhythmias occurring in these subjects because mental stress–induced arrhythmias are relatively uncommon in young healthy subjects, particularly in response to the mild stress used in these studies. In patients with abnormal hearts, however, where the additional substrate such as scarring, fibrosis, and remodeling is present, mental stress–induced arrhythmias are common. The objective was to identify a mechanism that might be relevant to these hearts while avoiding the possible confounding influence of ischemia.
At present, there is no established parameter of the standard 12-lead EKG to quantify dispersion of ventricular repolarization. It is clear, though, that the latter cannot be reliably estimated by simple manually derived indices such as the visually assessed T-wave shape or QT dispersion. Although presently there are no clinical or experimental studies directly linking TWR, i.e., the nondipolar components of the T wave from the standard 12-lead EKG to repolarization heterogeneity, multiple circumstantial data point to the existence of such a link. Many studies with multiple electrode body surface potential mapping, both experimental as well as clinical, have demonstrated that although in healthy hearts both activation and recovery generally follow a uniform dipolar pattern, in diseased hearts or during interventions that increase electrical heterogeneity, the pattern of activation and recovery changes towards multipolarity (29,40–44). The nondipolar T-wave components of the standard 12-lead EKG are significantly increased in various cardiac patients compared with healthy controls (12,45,46), differ significantly between healthy men and women, and follow a circadian pattern similar to the pattern of frequency of cardiac events (28) and have independent prognostic value for total mortality (14). More than 25 years ago, Abildskov et al. suggested that the nondipolar EKG components might provide the key to the information about local electrical events hidden in the surface EKG and hence to the risk of arrhythmias (47). Experimental studies are needed to directly address the link between repolarization heterogeneity and the nondipolar T-wave components from the 12-lead EKG, similar to the studies with perfused wedge preparation, which demonstrated the cellular mechanism of T-wave alternans (48). So far, no study has compared TWR measured from multiple electrode body surface potentials with those measured from standard 12-lead EKGs. At present, very few studies have investigated TWR from the standard 12-lead EKG, and therefore only limited quantitative data are available about their range of normal values and the effect of them on different physiological or pathophysiological factors.
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CONCLUSIONS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSNOTESREFERENCES |
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We are grateful to the following Medical Hypnotists for their help with the hypnosis protocols: Peter Mabbutt, D. Hyp(Dist), FBSCH; Amanda Bond, D. Hyp, FBSCH; Sarah Longmore, D. Hyp, PDCHyp, MBSCH, Dip Psych Couns, BSc(Hons), BA(Hons); Phil Benjamin, D. Hyp, PDCHyp, MBSCH; and Maureen Kiely, BSc(Hons), Dip. RWTA, D. Hyp(Dist), PDCHyp, MBSCH.
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NOTES |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSNOTESREFERENCES |
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There are no financial associations that might pose a conflict of interest in connection with the submitted article. This work was supported in part by a grant from the British Heart Foundation (V.B., K.H.).
DOI:10.1097/01.psy.0000160463.10583.88
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONSNOTESREFERENCES |
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ek BM, Smith ER. Vulnerability to ventricular arrhythmia: assessment by mapping of body surface potentials. Circulation 1986;73:684–92.This article has been cited by other articles:
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  R. C. Ziegelstein Acute Emotional Stress and Cardiac Arrhythmias JAMA, July 18, 2007; 298(3): 324 - 329. [Abstract] [Full Text] [PDF]
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 M. A. Gray, P. Taggart, P. M. Sutton, D. Groves, D. R. Holdright, D. Bradbury, D. Brull, and H. D. Critchley A cortical potential reflecting cardiac function PNAS, April 17, 2007; 104(16): 6818 - 6823. [Abstract] [Full Text] [PDF]
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