Download Posture and Gender Differentially Affect Heart Rate Variability of

Acta Cardiol Sin 2016;32:467-476
Original Article
doi: 10.6515/ACS20150728B
General Cardiology
Posture and Gender Differentially Affect Heart
Rate Variability of Symptomatic Mitral Valve
Prolapse and Normal Adults
Chien-Jung Chang,1,2 Ya-Chu Chen,1 Chih-Hsien Lee,1,3 Ing-Fang Yang4 and Ten-Fang Yang1,5
Background: Heart rate variability (HRV) has been shown to be a useful measure of autonomic activity in healthy
and mitral valve prolapsed (MVP) subjects. However, the effects of posture and gender on HRV in symptomatic
MVP and normal adults had not been elucidated in Taiwan.
Methods: A total of 118 MVP patients (7 males, 39 ± 7 years old; and 111 females, 42 ± 13 years old) and 148
healthy control (54 males, 28 ± 4 years old; and 94 females, 26 ± 6 years old) were investigated. The diagnosis of
MVP was confirmed by cross-sectional echocardiography. A locally developed Taiwanese machine was used to
record the HRV parameters for MVP and control groups in three stationary positions. Thereafter, the HRV
time-domain parameters, and the frequency-domain parameters derived from fast Fourier transform or
autoregressive methods were analyzed.
Results: The MVP group showed a decrease in time domain parameters and obtunded postural effects on
frequency domain parameters moreso than the control group. Though the parasympathetic tone was dominant in
female (higher RMSSD, nHF and lower nLF vs. male), the sympathetic outflow was higher in MVP female (lower
SDNN, NN50 and higher nLF vs. normal female). While the parasympathetic activity was lower in male,
sympathetic outflow was dominant in MVP male (lower nHF and higher nLF vs. normal male).
Conclusions: Both MVP female and male subjects had elevated levels of sympathetic outflow. The obtunded
postural effects on frequency domain measures testified to the autonomic dysregulation of MVP subjects.
Key Words:
Arrhythmia · Autonomic nerve system · Heart rate variability · Mitral valve prolapse
INTRODUCTION
heart disease characterized by the displacement of an
abnormally thickened mitral valve leaflet in the left
atrium during cardiac systole as a result of redundant
leaflets or chordate tendinea. 1,2 It is well-known that
MVP is a heterogeneous disorder with varieties of
pathological, clinical and echocardiographic manifestations.3,4 The overall prognosis of patients with MVP is
excellent, but a small subset develops serious complications including pronounced mitral regurgitation, embolic stoke, infective endocarditis, and arrhythmia.5 It
has been reported that MVP patients, especially when
symptomatic, have an autonomic dysfunction which
probably involves both the sympathetic and parasympathetic systems. A predominant sympathetic tone and diminished vagal activity in these patients is linked to the
Mitral valve prolapse (MVP) is a common valvular
Received: March 7, 2015
Accepted: July 28, 2015
1
Department of Biological Science and Technology, National Chiao
Tung University, Hsinchu; 2Division of Cardiology; 3Department of
Cardiac Surgery, Tungs’ Taichung Metroharbor Hospital, Taichung;
4
Department of Internal Medicine, Jen-Chi General Hospital; 5Graduate
Institute of Medical Informatics, Department of Internal Medicine,
Taipei Medical University and Hospital, Taipei, Taiwan.
Address correspondence and reprint requests to: Dr. Ten-Fang Yang,
Department of Biological Science and Technology, National Chiao
Tung University, Hsinchu; Graduate Institute of Medical Informatics,
Taipei Medical University, No. 250, Wu-Xin Street, Taipei City 110
Taiwan. Tel: 886-2-2736-1661 ext. 3351; Fax: 886-2-2733-9049;
E-mail: [email protected] or [email protected]
467
Acta Cardiol Sin 2016;32:467-476
Chien-Jung Chang et al.
male with or without MVP would present a variety of
autonomic modulations.
Therefore, our study aimed to compare the autonomic balance of three different stationary postures between males and females, with or without MVP, based
on short-term HRV analysis. In addition, we also tested
the correlation between parameters measured by FFT
and AR methods, respectively.
pathogenesis of the disease and a consequence of
emerging symptoms.6 Thus, finding a feasible modality
to analyze the autonomic nervous system (ANS) of MVP
victims seems to be of particular clinical importance.
Previous experimental evidence suggests that heart
rate variability (HRV) is one of the useful methods in
evaluating the autonomic modulation of the heart to
quantify risk in a wide variety of both cardiac and noncardiac disorders.7,8 HRV measures the variations of the
time intervals between consecutive heartbeats, which
vary mostly under control of the ANS. 9,10 When the
parasympathetic system is dominant, the heartbeat intervals oscillate with higher frequencies. When sympathetic arousal occurs, lower frequency oscillations take
place. A decreased HRV reflects enhanced sympathetic
overdrive and decreased vagal activity, which has a
strong association with the pathogenesis of cardiac
arrhythmias in the general population, and especially in
cardiac patients.11,12
There are two main methods utilized to express
HRV, which are the time domain and the frequency domain parameters. T ime domain indices are based on
normal-to-normal beat intervals and are closely related
to frequency domain HRV.13 Frequency domain parameters derived from either fast Fourier transform (FFT) or
autoregressive (AR) analyses provided a similar but subtle different discriminating power, respectively.7,14,15
A gender difference in the ANS activities had been
reported due to developmental dissimilarities, the plasma
level of norepinephrine and the effects of prevailing
levels of sex hormones. Studies of gender differences in
autonomic regulation demonstrate that women have
significantly greater parasympathetic input to cardiac
regulation than do age-matched men.16-18 In contrast, a
study of women with the MVP syndrome demonstrated
an autonomic dysfunction with decreased parasympathetic and increased adrenergic activities than control.19
Therefore, previous studies examining gender differences in healthy populations report contradictory findings from MVP victims. Furthermore, ANS is also affected by different stationary postures (e.g. lying down,
sitting and standing) which modulate the balance of
sympathetic and parasympathetic input of the heart.
Parasympathetic nerves are more active in the lying position, and sympathetic nerves are augmented in an
orthostatic position. A change of posture in male or feActa Cardiol Sin 2016;32:467-476
MATERIALS AND METHODS
Subjects
Patients who had disorders such as ischemic or
rheumatic heart disease, diabetes mellitus, thyroid disorders, stenotic valvular heart disease, severe left ventricular dysfunction, patients taking drugs affecting cardio-respiratory responses or alcohol were excluded (Table 1). All subjects were asked to avoid smoking and
drinking any caffeinated beverages during the study. The
protocol was consistent with the ethical guidelines of
the Research Committee of Taipei Medical University
and the relevant standards of the revised Declaration of
Helsinki (1983). All participants gave informed consent.
Table 1. Patient characteristics
MVP
male
(n = 7)
MVP
Normal
female
male
(n = 111) (n = 54)
Normal
female
(n = 94)
Age (yrs)*
39 ± 7 042 ± 13 28 ± 4
26 ± 6
MR
(+)
(+)
(-)
(-)
LA (mm)*
36 ± 4
34 ± 3
30 ± 6
31 ± 5
LVEDD (mm)*
46 ± 5
41 ± 4
43 ± 6
40 ± 4
LVESD (mm)*
24 ± 4
25 ± 5
25 ± 6
23 ± 5
LV EF (%)*
67 ± 7
68 ± 8
61 ± 6
68 ± 7
Duabetes mellitus
–
–
–
–
Hypertension
–
–
–
–
Systolic BP (mmHg)* 125 ± 10 119 ± 50 111 ± 11 108 ± 70
Diastolic BP (mmHg)* 068 ± 13 066 ± 15 076 ± 16 71 ± 8
ALT (U/L)*
36 ± 3
35 ± 4
34 ± 3
36 ± 4
Creatinine (mg/dl)* 00.9 ± 0.4 00.7 ± 0.5 01.0 ± 0.3 00.8 ± 0.4
* Values are mean ± SD.
ALT, alanine aminotransferase; Diastolic BP, diastolic blood
pressure; LA, left atrial diameter; LVEDD, left ventricular enddiastolic diameter; LV EF, ejection fraction of left ventricle;
LVESD, left ventricular end-systolic diameter; MR, mitral
regurgitation; MVP, mitral valve prolapsed; SD, standard
deviation; Systolic BP, systolic blood pressure.
468
Posture and Gender on HRV of MVP and Normal Adults
A total of 118 MVP patients (7 males, 39 ± 7 years old
and 111 females, 42 ± 13 years old) who had been diagnosed with MVP after evaluation by transthoracic echocardiography at Taipei Medical University Hospital cardiology clinic from November 2008 to January 2013.
Another 148 healthy control (54 males, 28 ± 4 year-old
and 94 females, 26 ± 6 year-old) who had normal 12lead electrocardiogram (ECG) without previous history
of medical disease from National Chiao-Tung University
and residents in Hsinchu were recruited for the study.
pean Society of Cardiology and the North American Society of Pacing and Electrophysiology standards for measurement of HRV.7 The QRS complexes were detected
and labeled automatically by the machine. The results of
the automatic analysis were reviewed subsequently and
the errors in R-wave detection or R-R were manually
corrected for ectopic/missed beats. In the present study,
manual editing or interpolation of the R-R intervals was
performed using the following guidelines: if a significantly higher R-R interval (representing an ectopic beat)
was noted, then that reading was deleted and the average of the two adjacent R-R intervals replaced the deleted one. If a significantly lower value (representing a
missed beat) was noted, that R-R interval was deleted
and replaced with the previous R-R interval. Once the
R-R intervals were imported into the computed program, the software automatically analyzed the HRV in
both time and frequency domains.
Echocardiography
In all subjects, transthoracic two-dimensional and
Doppler echocardiographic examinations were performed
by experienced echocardiographers, using a V ivid 7
echocardiographic system (General Electric Ultrasound,
US), using 2.5-3.5 MHz transducers. The measurements
were obtained according to the standards of the American Society of Echocardiography, using the parasternal
long axis and apical 4-chamber windows. The diagnosis
of MVP was confirmed by cross-sectional echocardiography that showed definite prolapse (posterior/superior displacement) of anterior and/or posterior leaflet of
the mitral valve beyond the plane of mitral annulus in
the parasternal long-axis view and apical 4-chamber
view. Prolapse of a leaflet in the apical 4-chamber view
alone was excluded because of frequent false positive
diagnoses due to non-planar or saddle-shaped mitral
annulus. Classic prolapse was defined as superior displacement of the mitral leaflets, by more than 2 mm
during systole, with a maximal leaflet thickness of at
least 5 mm during diastole.2-4
Analysis of HRV
HRV was assessed automatically by the machine
from the calculation of the mean R-R interval and its
standard deviation measured on short-term (5 minutes)
electrocardiogram, normal-to-normal (NN) R-R interval
data obtained from the edited time sequence of R-wave
and QRS labeling were then transferred to a personal
computer. The SDNN, RMSSD and NN50 were used for
comparison of time-domain parameters.
For frequency domain HRV parameters analysis,
spectral power was quantified by FFT and AR methods
for the following frequency bands: total power (TP, †
0.4Hz), very low frequency (VLF, 0.003-0.04Hz), low frequency (LF, 0.04-0.15Hz), high frequency (HF, 0.15-0.4
Hz), normalized low frequency (nLF), normalized high
frequency (nHF) and LF/HF ratio. These parameters
were defined in accordance with the 1996 ACC/AHA/
ESC consensus.7
HRV recordings
All the subjects were asked to rest for five minutes
before each HRV recording (lying, sitting and standing).
The recordings were all taken during the daytime (between 9:00 AM to 4:00 PM) to avoid the diurnal influence of the autonomic regulation. A locally developed
Taiwanese machine (DailyCare BioMedical’s ReadMyHeart) was used to record the HRV parameters. One
lead ECG (modified lead II, put the pad one on right
shoulder and the other on left flank) was used for signal
collection and analysis. The data were then exported as
a text file to the HRV analysis software complying with
guidelines recommended by the Taskforce of the Euro-
Statistical analysis
All HRV data were expressed as mean ± standard
deviation (SD) and % ratio. A one-way repeated-measures analysis of variance (ANOVA) followed by Tukey’s
post-hoc test was used to characterize changes in HRV
variables between three stationary positions. The parameters between two groups were compared using Student’s t-test, and the normal distribution was proven by
469
Acta Cardiol Sin 2016;32:467-476
Chien-Jung Chang et al.
adults. The similar postural effects were also found in
MVP subjects except that the sitting position cannot decrease the TP in MVP subjects as it did in normal adults.
Furthermore, FFT and AR methods show similar postural
effects on all frequency-domain parameters in normal
and MVP subjects. As shown in Figure 2B, the MVP subjects had lower TP in the lying position, but had higher
TP in the sitting and standing position. MVP subjects
also had higher nHF, lower nLF and LF/HF parameters in
the sitting and standing positions. Both FFT and AR
methods show similar results of all frequency domain in
normal and MVP subjects.
Kolmogorov-Smirnov test. A p value of < 0.05 was considered as statistically significant in all cases.
RESULTS
Postural effect on time domain parameters
As shown in Figure 1A, standing position decreased
the SDNN, RMSSD and NN50 of normal adults and MVP
subjects as compared with those parameters in the lying
position, whereas sitting position also decreased RMSSD
of normal adults and MVP subjects as compared with
that in the lying position. The MVP subjects had decreased SDNN in all three positions, decreased RMSSD
in sitting posture, and decreased NN50 in lying and sitting position as compared with normal adults, as shown
in Figure 1B.
Gender difference on time domain parameters
As shown in Figure 3A, normal and MVP female subjects had higher RMSSD and NN50 than male in a lying
position. As shown in Figure 3B, MVP male had lower
SDNN, RMSSD and NN50 in the lying position, lower
RMSSD and NN50 in the sitting position than the normal
male. Meanwhile, MVP females had lower SDNN in the
sitting position and lower NN50 in both the lying and
sitting positions than normal female.
Postural effect on frequency domain parameters
As shown in Figure 2A, both sitting and standing position decreased the TP and nHF, and increased the nLF
and LF/HF ratio as compare with lying position in normal
A
B
Figure 1. Postural effects on time domain parameters in normal and MVP subjects. (A) Postural effects on SDNN, RMSSD and NN50 in normal
adults (n = 148) and MVP subjects (n = 118). * p < 0.05, # p < 0.01, vs. lying position. (B) Comparison of SDNN, RMSSD and NN50 between normal (n =
148) and MVP subjects (n = 118). * p < 0.05, # p < 0.01, vs. normal adults. MVP, mitral valve prolapsed.
Acta Cardiol Sin 2016;32:467-476
470
Posture and Gender on HRV of MVP and Normal Adults
A
B
Figure 2. Postural effect on frequency domain parameters in normal and MVP subjects. (A) Postural effects on TP, nHF, nLF and LF/HF in normal
adults (n = 148) and MVP subjects (n = 118) by FFT or AR methods, respectively. * p < 0.05, # p < 0.01, vs. lying position. (B) Comparison of TP, nHF,
nLF and LF/HF s between normal (n = 148) and MVP subjects (n = 118) by FFT or AR methods, respectively. * p < 0.05, # p < 0.01, vs. normal adults.
AR, autoregressive; FFA, fast Fourier transform; nLF, normalizedlow frequency; nHF, normalized high frequency; TP, total power; MVP, mitral valve
prolapsed.
Gender difference on frequency domain parameters
As shown in Figure 4A, both FFT and AR methods revealed that normal female had higher nHF, lower nLF
and LF/HF than normal male in all three positions. As
shown in Figure 4B, both FFT and AR methods revealed
that MVP female had higher nHF and lower nLF than
MVP male in all three positions. FFT method showed
MVP female had lower LF/HF than MVP male in both lying and sitting positions, but AR method showed MVP
female had lower LF/HF than MVP male in lying position.
thod. Both FFT and AR showed MVP male had higher
nLF in the lying position, higher LF/HF in the lying position and lower LF/HF in the sitting and standing positions. As shown in Figure 5B, both FFT and AR showed
identical result in female subjects. MVP female had decreased TP in all three positions than the normal female
had. There were no nHF and LF/HF differences in all
three positions between normal and MVP females, but
MVP female had increased nLF in the lying position.
DISCUSSION
MVP effects on frequency domain parameters
As shown in Figure 5A, both FFT and AR showed a
similar result in male subjects. MVP male had a lower TP
in all three positions and lower nHF in the lying position.
FFT method revealed that MVP male also had lower nHF
in the sitting position, which was not found by AR me-
The present study revealed distinct postural effects
and gender differences on autonomic function between
MVP subjects and normal control. Since orthostatic posture often involves activation and/or inhibition of either
component of the autonomic nervous system, it is use471
Acta Cardiol Sin 2016;32:467-476
Chien-Jung Chang et al.
A
B
Figure 3. Gender difference on time domain parameters in normal and MVP subjects. (A) Comparison of SDNN, RMSSD and NN50 between male
and female in normal or MVP subjects, respectively. * p < 0.05, # p < 0.01, vs. male. (B) Comparison of SDNN, RMSSD and NN50 between normal and
MVP subjects in male or female, respectively. * p < 0.05, # p < 0.01, vs. normal subjects.
ful to categorize the abnormal autonomic response and
potential cardiac risk in each gender of MVP patients.
The first major finding was that a standing posture favored the sympathetic activity (decreased SDNN and
NN50) and the orthostatic position (sitting and standing) attenuated parasympathetic outflow (decreased
RMSSD) in both normal and MVP subjects (Figure 1A),
Acta Cardiol Sin 2016;32:467-476
whereas MVP subjects possess higher sympathetic tone
(smaller SDNN and NN50) and lower parasympathetic
activity (lower RMSSD) than normal control (Figure 1B).
The second major finding indicated that orthostatic decreased parasympathetic outflow (lower TP and nHF),
and increased sympathetic tone (higher nLF and LF/HF)
were also found by frequency domain in normal and
472
Posture and Gender on HRV of MVP and Normal Adults
A
B
Figure 4. Gender difference on frequency domain parameters in normal or MVP subjects. (A) Comparison of TP, nHF, nLF and LF/HF between male
and female in normal subjects by FFT or AR methods, respectively. (B) Comparison of TP, nHF, nLF and LF/HF between male and female in MVP subjects by FFT or AR methods, respectively. * p < 0.05, # p < 0.01, vs. male. Abbreviations are in Figure 2.
MVP subjects (Figure 2A). MVP victims had higher sympathetic tone (lower TP) in the lying position, but lower
sympathetic tone (higher TP and nHF, lower LF/HF) in
the sitting and standing position than normal adults
(Figure 2B). The third major finding was that both normal and MVP females had higher parasympathetic tone
(higher RMSSD and NN50) than male in the lying position (Figure 3A). MVP male had high sympathetic and
low parasympathetic tone (lower SDNN, NN50 and
RMSSD) in the lying position than normal male. MVP female had higher sympathetic tone (lower SDNN and
NN50) in sitting position than normal female (Figure
3B). The fourth major finding was that normal and MVP
female had higher parasympathetic and lower sympathetic tone (higher nHF, lower nLF) than normal and
MVP male (Figure 4). Lastly, the fifth major finding was
that MVP male had a higher sympathetic and lower
parasympathetic tone (lower TP, higher nLF and lower
nHF) than normal male in lying position. However, MVP
male had lower sympathetic tone (lower LF/HF) in the
sitting and standing positions (Figure 5A). MVP female
had increased sympathetic tone (lower TP, higher nLF)
than normal female (Figure 5B).
In brief, MVP subjects had higher sympathetic and
lower parasympathetic activity. Orthostatic posture significantly increased the sympathetic tone in normal
adults, but not in MVP subjects. This novel finding indicates an obtunded sympathetic response to orthostatic
position in MVP subjects, which was found particularly
in MVP male. MVP male had higher sympathetic outflow, meanwhile MVP female had higher parasympathetic tone. However, MVP female possesses higher
sympathetic outflow than normal female. The mechanisms underlying the gender difference in cardiac autonomic function has not been fully elucidated. It has
been proposed that middle-aged women and men have
a more dominant parasympathetic and sympathetic regulation of heart rate, respectively. The gender-related
473
Acta Cardiol Sin 2016;32:467-476
Chien-Jung Chang et al.
A
B
Figure 5. MVP effects on frequency domain parameters in male or female. (A) Comparison of TP, nHF, nLF and LF/HF between normal and MVP in
male subjects. * p < 0.05, # p < 0.01, vs. normal subjects. (B) Comparison of TP, nHF, nLF and LF/HF between normal and MVP in female subjects. * p <
0.05, # p < 0.01, vs. normal subjects. Abbreviations are in Figure 2.
toms. 24 Abnormal autonomic regulation has been reported to be responsible for symptomatic subjects with
a complex of presenting symptoms such as elevated circulating concentrations of catecholamines and enhanced b receptor affinity, suggesting the existence of a
hyperadrenergic state, diminished vagal tone and other
autonomic malfunctions.24,25 Similar to previous reports,
our finding in patients with MVP indicated decreased
parasympathetic activity in addition to abnormal adrenergic activity and response, which potentiate the occurrence of clinical symptoms and arrhythmogenesis.26-30
Autonomic imbalance indicated by HRV may contribute to disease progression, is an indicator of disease
pathogenesis, and is a better predictor of poor prognosis than other hemodynamic measures in cardiac diseases. Autonomic dysregulation may also be a key determinant in the origin and progression of MVP, thus our
finding not only accounts for the clinical symptoms and
progression of valvular insufficiency but also has future
difference in parasympathetic regulation diminishes after 50 years of age, whereas a significant time delay for
the disappearance of sympathetic dominance occurs in
men.20 Our studies of gender differences in autonomic
regulation demonstrate significantly greater parasympathetic activity in women, which further depict an underlying cardioprotective mechanism in females before
menopause.
MVP affects up to 2.4% of the general population
and has a benign course with excellent prognosis for
most patients.21,22 However, a minority of patients develops significant complications, including infective
endocarditis, cerebrovascular events, progressive MR,
and sudden cardiac death.5,6,12,23 MVP usually associated
with the coexistence of symptoms that cannot be explained on the basis of valvular regurgitation alone.
These various accompanying symptoms comprise palpitations, orthostatic rhythm disturbances, atypical chest
pain, exertional dyspnea and neuropsychiatric sympActa Cardiol Sin 2016;32:467-476
474
Posture and Gender on HRV of MVP and Normal Adults
implications for pharmaceutical and mechanical treatment.
Though the FFT and AR methods resulted in a comparable frequency-domain analysis in our MVP and normal subjects, FFT appears to have showed a bit higher
sensitivity in a short-term recording.
4.
5.
Study limitations
Our study did have several limitations. One limitation was that the respiratory rate was not controlled
when measuring the interbeat intervals over the fiveminute recording period. Research has shown that the
reliability of HRV measures was increased when respiratory rate was regulated. Furthermore, part of the intrasubject variability was also due to the natural change of
HRV parameters that occurs under the influence of factors such as mood, alertness and mental activity, which
are very difficult to control for in any study. In addition,
subjects were enrolled in a district general hospital and
a university, respectively, and they are not perfectly age
and sex matched. HRV derived from the short-term five
minute ECG recording, although it has been claimed to
be highly correlated to the 24-hour ECG recording, their
clinical value needs to be further studied. Besides, we
cannot exclude the impacts of circadian variation since
the HRV signals were collected from 9:00 A.M. to 4:00
P.M. The unadjusted age, height and weight might (BMI)
also affect the HRV data.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
CONCLUSIONS
In this investigation, we found that the normal female subjects were dominated by parasympathetic activity, whereas MVP female and male had prevailing
levels of sympathetic outflow. The obtunded postural
effects on frequency domain measures underscored the
autonomic dysregulation of MVP subjects.
16.
REFERENCES
19.
17.
18.
1. Heyek E, Gring GN, Griffin BP. Mitral valve prolapsed. Lancet
2005;365(9458):507-18.
2. Perloff JK, Child JS. Mitral valve prolapse: evolution and refinement of diagnostic techniques. Circulation 1989;80:710-1.
3. Levine RA, Stathogiannis E, Newell JB, et al. Reconsideration of
20.
21.
475
echocardiographic standards for mitral valve prolapse: lack of association between leaflet displacement isolated to the apical
four chamber view and independent echocardiographic evidence of abnormality. J Am Coll Cardiol 1988;11:1010-9.
Helmcke F, Nanda NC, Hsiung MC, et al. Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation
1987;75:175-83.
Boudoulas H, Schaal SF, Stang JM, et al. Mitral valve prolapse:
cardiac arrest with long-term survival. Int J Cardiol 1990;26:
37-44.
Stefanadis C, Toutouzas P. Mitral valve prolapse: the merchant of
Venice or much ado about nothing? Eur Heart J 2000;21:255-8.
Heart rate variability: standards of measurement, physiological
interpretation and clinical use. Circulation 1996;93:1043-65.
Kleiger RE, Stein PK, Bigger JT Jr. Heart rate variability: measurement and clinical utility. Ann Noninvasive Electrocardiol 2005;
10:88-101.
Kochiadakis GE, Parthenakis FI, Zuridakis EG, et al. Is there increased sympathetic activity in patients with mitral valve prolapse? Pacing Clin Electrophysiol 1996;19:1872-6.
Strano S, De Castro S, Ferrucci A, et al. Modification of the
sympathovagal interaction in mitral valve prolapse syndrome.
Evaluation of heart rate variability by spectrum analysis. Cardiologia 1992;37:755-60.
Chesler E, King RA, Edwards JE. The myxomatous mitral valve and
sudden death. Circulation 1983;67:632-9.
Chugh SS, Kelly KL, Titus JL. Sudden cardiac death with apparently normal heart. Circulation 2000;102:649-54.
Ori Z, Monir G, Weiss J, et al. Heart rate variability. Frequency domain analysis. Cardiol Clin 1992;10:499-537.
Moak JP, Goldstein DS, Eldadah BA, et al. Supine low-frequency
power of heart rate variability reflects baroreflex function, not
cardiac sympathetic innervation. Cleve Clin J Med 2009;76(Suppl
2):S51-9.
Vanderlei LC, Pastre CM, Hoshi RA, et al. Basic notions of heart
rate variability and its clinical applicability. Rev Bras Cir Cardiovasc 2009;24:205-17.
Kuo T, Lin T, Yang C, et al. Effect of aging on gender differences in
neural control of heart rate. Am J Physiol Heart Circ Physiol
1999;277:H2233-9.
Rossy L, Thayer J. Fitness and gender-related differences in heart
period variability. Psychosom Med 1998;60:773-81.
Umetani K, Singer D, McCraty R, Atkinson M. Twenty-four hour
time domain heart rate variability and heart rate: relations to
age and gender over nine decades. J Am Coll Cardiol 1998;31:
593-601.
Gaffney FA, Karlsson ES, Campbell W, et al. Autonomic dysfunction in women with mitral valve prolapse syndrome. Circulation
1979;59:894-901.
Tanaka M, Kimura T, Goyagi T, Nishikawa T. Gender differences in
baroreflex response and heart rate variability in anaesthetized
humans. British Journal of Anaesthesia 2004;92:831-5.
Playford D, Weyman AE. Mitral valve prolapse: time for a fresh
Acta Cardiol Sin 2016;32:467-476
Chien-Jung Chang et al.
look. Rev Cardiovasc Med 2001;2:73-81.
22. Savage DD, Garrison RJ, Devereux RB, et al. Mitral valve prolapsed in the general population. 1. Epidemiologic features: the
Framingham Study. Am Heart J 1983;106(3):571-6.
23. Zuppiroli A, Rinaldi M, Kramer-Fox R, et al. Natural history of mitral valve prolapse. Am J Cardiol 1995;75:1028-32.
24. Pasternac A, Tubau JF, Puddu PE, et al. Increased plasma catecholamine levels in patients with symptomatic mitral valve
prolapse. Am J Med 1982;73:783-90.
25. Davies AO, Mares A, Pool JL, Taylor AA. Mitral valve prolapse with
symptoms of beta-adrenergic hypersensitivity. Beta 2-adrenergic
receptor supercoupling with desensitization on isoproterenol
exposure. Am J Med 1987;82:193-201.
26. Maron BJ, Isner JM, McKenna WJ. 26th Bethesda Conference:
recommendations for determining eligibility for competition in
athletes with cardiovascular abnormalities. Task Force 3: hyper-
Acta Cardiol Sin 2016;32:467-476
27.
28.
29.
30.
476
trophic cardiomyopathy, myocarditis, and other myopericardial
diseases and mitral valve prolapse. Med Sci Sports Exerc 1994;
26:261-7.
Corrado D, Basso C, Rizzoli G, et al. Does sport activity enhance
the risk of sudden death in adolescents and young adults? J Am
Coll Cardiol 2003;42:1959-63.
Gaffney FA, Karlsson ES, Campbell W, et al Autonomic dysfunction in women with mitral valve prolapse syndrome. Circulation
1979;59:894-901.
Chesler E, Weir EK, Braatz GA, et al. Normal catecholamine and
hemodynamic responses to orthostatic tilt in subjects with mitral valve prolapse. Correlation with psychologic testing. Am J
Med 1985;78:754-60.
Lenders JW, Fast JH, Blankers J, et al. Normal sympathetic neural
activity in patients with mitral valve prolapse. Clin Cardiol 1986;
9:177-82.