Changes of deceleration and acceleration capacity of heart rate in patients with acute hemispheric ischemic stroke
Clinical Interventions in Aging
Changes of deceleration and acceleration capacity of heart rate in patients with acute hemispheric ischemic stroke
Yan-hong Xu 1 2
Xing-De Wang 0 1
Jia-Jun Yang 1 2
li Zhou 0 1
Yong-Chao Pan 1 2
0 Department of Cardiology, s hanghai Jiao Tong University Affiliated s ixth People's h ospital , s hanghai, People's republic of China
1 Xing-De Wang Department of Cardiology, shanghai Jiao Tong University Affiliated Sixth People's hospital , 600 Yishan road, shanghai 200233, People's republic of China Tel
2 Department of n eurology
Background and purpose: Autonomic dysfunction is common after stroke, which is correlated
with unfavorable outcome. Phase-rectified signal averaging is a newly developed technique for
assessing cardiac autonomic function, by detecting sympathetic and vagal nerve activity
separately through calculating acceleration capacity (AC) and deceleration capacity (DC) of heart
rate. In this study, we used this technique for the first time to investigate the cardiac autonomic
function of patients with acute hemispheric ischemic stroke.
Methods: A 24-hour Holter monitoring was performed in 63 patients with first-ever acute ischemic
stroke in hemisphere and sinus rhythm, as well as in 50 controls with high risk of stroke. DC, AC,
heart rate variability parameters, standard deviation of all normal-to-normal intervals (SDNN),
and square root of the mean of the sum of the squares of differences between adjacent
normalto-normal intervals (RMSSD) were calculated. The National Institutes of Health Stroke Scale
(NIHSS) was used to assess the severity of stroke. We analyzed the changes of DC, AC, SDNN,
and RMSSD and also studied the correlations between these parameters and NIHSS scores.
Results: The R–R (R wave to R wave on electrocardiogram) intervals, DC, AC, and SDNN in
the cerebral infarction group were lower than those in controls (P=0.003, P=0.002, P=0.006,
and P=0.043), but the difference of RMSSD and the D-value and ratio between absolute value
of AC (|AC|) and DC were not statistically significant compared with those in controls. The DC
of the infarction group was significantly correlated with |AC|, SDNN, and RMSSD (r=0.857,
r=0.619, and r=0.358; P=0.000, P=0.000, and P=0.004). Correlation analysis also showed that
DC, |AC|, and SDNN were negatively correlated with NIHSS scores (r=−0.279, r=−0.266, and
r=−0.319; P=0.027, P=0.035, and P=0.011).
Conclusion: Both DC and AC of heart rate decreased in patients with hemispheric infarction,
reflecting a decrease in both vagal and sympathetic modulation. Both DC and AC were
correlated with the severity of stroke.
Keywords: acute ischemic stroke, autonomic dysfunction, deceleration capacity of heart rate,
acceleration capacity of heart rate, heart rate variability
Stroke has become the leading cause of death in the People’s Republic of China1 and
the second most common cause of death worldwide.2 Cardiac autonomic
dysfunction is common after stroke, which is correlated with unfavorable outcome.3,4 As an
electrophysiological method, heart rate variability (HRV) has been used to assess the
autonomic function for decades. Studies have shown that HRV is related to the severity
of stroke5 and has some mortality predictive values.6 However, it cannot accurately
distinguish the sympathetic and vagal nerve activity. Phase-rectified signal averaging
Clinical Interventions in Aging 2016:11 293–298 293
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(PRSA) is a newly developed technique for detecting cardiac
autonomic function, which can quantitatively detect the
function of vagal and sympathetic nerves by calculating the
deceleration capacity (DC) and acceleration capacity (AC)
of the heart, respectively. Its advantages have been shown
in the field of cardiology.7 However, this method has not
yet been used in the study of autonomic dysfunction after
stroke. In this study, the changes in DC and AC of heart rate
and other related parameters were studied in patients with
acute cerebral infarction for the purpose of investigating
their values in assessing the autonomic function of patients
Materials and methods
A total of 63 patients (38 men and 25 women; mean age,
71±12 years) with first-ever acute cerebral infarction and
sinus rhythm were recruited within 72 hours after stroke.
.vdoepw l.syeon raphy (CT) scan confirmed the infarction located in the
A magnetic resonance imaging (MRI) or computed
://sw lona cerebral hemispheres, with 35 in the left hemisphere and 28
h ep in the right. Patients with manifestations of other nervous
from roF system lesions and patients with any other diseases or
medied cation known to affect the autonomic nervous system were
lado excluded. Patients with tumor, infection, previous heart, or
onw pulmonary disease were also excluded.
ignd A total of 50 controls (24 men and 26 women; mean age,
gA 68±11 years) were recruited from subjects with high risk of
isnn stroke but without history of stroke. Patients who had two or
itno more of the following major risk factors, or one major risk
trvee factor, and two or more secondary risk factors were defined
lIna as patients with high risk of stroke. Major risk factors include
ilicn 1) hypertension, 2) hyperlipidemia, 3) diabetes mellitus,
C 4) age .50 years, and 5) metabolic syndrome; secondary risk
factors include 1) atrial fibrillation or heart disease, 2)
smoking, 3) family history of stroke or heart attack, 4) obesity,
5) regular alcohol consumption, 6) lack of physical exercise,
7) dietary excess oil, 8) sleep apnea, 9) male, 10) often gums
bleeding, teeth loose, or loss, 11) ischemic ophthalmopathy,
and 12) sudden deafness. MRI was used in the control group
to exclude acute infarction. The other exclusion criteria were
the same as for the stroke group.
We obtained oral informed consent from both patients
and controls or their clients. This study was approved by
the ethics committee of Shanghai Jiao Tong University
Affiliated Sixth People’s Hospital. Sex, age, and combined
basic diseases and conditions were not statistically different
between the two groups (Table 1).
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MRI was used to obtain the side and location information
of the infarction. If MRI was contraindicated or unable to
be obtained, repeat CT scans were used in order to identify
the exact location of infarction. The National Institutes of
Health Stroke Scale (NIHSS) was used to record the
severity of neurologic deficit. An experienced neurologist was in
charge of this work.
Detection of autonomic parameters
All patients underwent a 24-hour Holter monitoring within
1 week after admission. The recordings were analyzed by
a DMS Holter system (DMS300-3; Diagnostic Monitoring
Software, Stateline, NV, USA). The interferences were
excluded, and the events of arrhythmia were tagged
artificially when playing back the recordings. The signal
processing technique of PRSA was used to process sequences of R–R
intervals obtained from the Holter recordings.8 This technique
provides separate characterizations of deceleration- and
acceleration-related modulations, quantified by DC and AC.
It is believed that DC reflects vagal activity and AC reflects
sympathetic activity of the heart. The computer calculated
DC and AC automatically. Meantime, standard deviation of
all normal-to-normal intervals (SDNN) and square root of
the mean of the sum of the squares of differences between
adjacent normal-to-normal intervals (RMSSD) were also
calculated through the 24-hour Holter recordings, which
were widely used parameters of HRV and were considered
to reflect overall variability and parasympathetic modulation
of the heart, respectively. As the values of AC were negative,
we used the absolute value of AC (|AC|) in the analyses. We
also calculated the D-value between |AC| and DC (|AC|−DC)
and the ratio of |AC| and DC (|AC|/DC) to reflect the balance
of sympathetic and parasympathetic modulation. The
electrophysiological analysts remained blinded to the clinical
data during the study period.
Mean values (± standard deviation [SD]) were calculated for
continuous variables. Distributions of continuous variables
were determined by the Shapiro–Wilk test. Group differences
were assessed by Student’s t-test or Mann–Whitney U-test.
Comparisons of categorical variables were made using
chisquare test or Fisher’s exact test. Correlations between
different autonomic parameters were calculated using Pearson’s
correlation test, and correlations between autonomic
parameters and NIHSS scores were calculated using Spearman rank
correlation test. Data analysis was performed using SPSS
Version 17.0 (SPSS Inc., Chicago, IL, USA). A value of
P,0.05 was considered statistically significant.
Comparison of autonomic parameters
between infarction patients and controls
Compared with controls, the R–R intervals, DC, AC, and
SDNN of the infarction group were lower. But the difference
of RMSSD, the D-value between |AC| and DC (|AC|−DC),
and the ratio of |AC| and DC (|AC|/DC) were not statistically
significant compared with controls (Table 1).
Comparison between left and right
Some autonomic parameters of patients with the right
hemispheric infarction were slightly lower than that of the
left, but the differences were not statistically significant
In the infarction group, DC correlated significantly with
|AC|, SDNN, and RMSSD. In 63 patients with stroke, NIHSS
scores ranged from 0 to 21 (6.52±5.68). There is a negative
correlation between NIHSS and DC, |AC|, and SDNN. No
significant correlation was identified between NIHSS scores
and RMSSD, the D-value between |AC| and DC, and the
ratio of |AC| and DC (Table 3; Figures 1–3).
Parameter Left infarction Right infarction P-value
nIhss 7.60±6.44 5.18±4.30 0.080
r–r intervals, ms 869.4±119.2 860.2±150.5 0.789
DC, ms 5.66±1.81 5.42±2.19 0.627
AC, ms −6.30±2.00 −5.75±2.05 0.288
sDnn, ms 93.40±29.98 92.82±32.94 0.942
rMssD, ms 27.49±12.91 24.25±10.93 0.295
|AC|–DC 0.633±0.962 0.329±1.184 0.265
|AC|/DC 1.132±0.243 1.194±0.751 0.646
Abbreviations: AC, acceleration capacity; DC, deceleration capacity; nIhss,
national Institutes of health stroke scale; rMssD, square root of the mean of
the sum of the squares of differences between adjacent normal-to-normal intervals;
sDnn, standard deviation of all normal-to-normal intervals; r–r intervals, r wave
to r wave intervals on electrocardiogram; |AC|, absolute value of AC.
Patients with stroke often complicate with cardiac autonomic
dysfunction, which can lead to a variety of cardiac
arrhythmias, T wave change, myocardial infarction, and even sudden
death.9 Cardiac involvement is an important cause of death after
stroke.10 Sympathetic hyperactivity and decrease in
parasympathetic activity caused by stroke may be the reason of arrhythmia
and sudden death. Studies found that cardiac autonomic
dysfunction was related to the location and severity of stroke4,5 and
may be related to the unfavorable outcome of stroke.6,11,12
HRV has been used to detect the cardiac autonomic
modulation for decades. However, it cannot distinguish the
sympathetic and vagus nerve activity. In addition, there is no
HRV parameter directly reflecting sympathetic modulation.13
Plasma catecholamine concentrations are usually used to
measure the function of sympathetic nerve. However, plasma
catecholamine concentrations are affected by many factors,
such as the release, distribution, metabolism, and excretion
of amines,14 and they are also affected by circadian rhythm.15
.375 PRSA is a new technique for detecting autonomic function.
/yb It can detect the AC and DC of the heart directly through
ana.com lyzing the overall trend of 24-hour heart rate, and thus it can
rsse quantitatively detect the sympathetic activity and vagus
activ.vdoepw l.syeon ity, respectively, at the same time.7,8 This technique has been
used mainly in the field of cardiovascular medicine, but not
//ww lau yet in the analysis of autonomic dysfunction after stroke.
tt:sp rson In our study, we found that DC and AC as well as SDNN
h ep were all lower than controls, reflecting both sympathetic and
from roF vagal modulation loss in patients with hemispheric infarction.
daed DC and AC were correlated with each other strongly, and the
lno D-value and the ratio of absolute value of AC and DC had
odw no significant difference compared with controls, reflecting
igng that there was no major change in sympathovagal balance in
inA patients with stroke. The loss of parasympathetic modulation
itvsneno iisn cAoCnsriestfelencttswaithdeHcrReVasestiundsieysm.3p,16atHheotwiceavcetri,vtihtye, dwehcircehasies
iaenccchtioovnliastymistioenfnetsctworoniktcheensittnruacdtriieoeansssec.d1o6n,1t7chIlrunoduthignehgclttihhneaitcd,teihnteeccrsteyiaomsnepdoabtfhlcoeatoitdcpressure, heart rate, and other characteristics of enhanced
sympathetic activity are common in patients with cerebral
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infarction. In our study, we also found that R–R intervals of
patients with infarction were shorter than those in controls,
which might be a reflection of sympathetic hyperactivity.
Our findings demonstrate a phenomenon that both the vagal
and sympathetic modulation decrease after stroke, but the
combined effects of the two result in predominant
sympathetic activity. This phenomenon could be explained by the
fact that the effect of heart rate increasing by decreased vagal
activity was larger than the effect of heart rate decreasing by
decreased sympathetic activity. The sympathetic activity is
relatively predominant rather than absolutely predominant.
The study results were not conclusive of whether the
lateralization and location of infarction were associated
with autonomic derangement. Most studies found that if the
infarctions are located in the right hemisphere especially with
insula involvement, the cardiac autonomic dysfunction was
more pronounced.4,18,19 In this study, autonomic parameters
of patients with left and right cerebral infarction were
compared. Although the autonomic parameters of patients with
right hemispheric infarction were slightly lower than those
of the left hemisphere, the differences were not statistically
significant. Due to limited sample size, patients with the
insula involvement were not analyzed separately. A further
study of a larger number of cases is needed to search for
the effect of lateralization and location of infarction on the
autonomic nervous system.
In this study, the NIHSS score was used to assess the
severity of stroke. Correlation analysis showed that DC,
absolute value of AC, and SDNN were negatively correlated with
NIHSS scores, which indicates a higher risk of autonomic
complications in patients with more severe stroke.5 Although
significant correlations between autonomic parameters and
NIHSS scores were found, the r values were rather low. We
assume that autonomic function is affected by many factors
such as age, sex, and combined diseases, which do not
influence the NIHSS scores directly. The infarction location
and lateralization also have different effects on autonomic
modulation and NIHSS scores.
Declining autonomic modulation predicts poor outcomes
in many diseases, such as myocardial infarction,20 chronic
heart failure,21 and ischemic stroke.6 Studies also showed that
vagus nerve had protective effects.22,23 The decline of vagal
modulation may decrease this protective effect. DC, which is
a direct reflection of vagal modulation, has shown its value in
predicting mortality after myocardial infarction.7 Our study
has also shown a decline in DC in patients with hemispheric
infarction. Further studies for the value of DC in prognosis
prediction in patients with stroke are deserved.
Both DC and AC decrease in patients with acute hemispheric
infarction, reflecting the loss of both parasympathetic and
sympathetic modulation after stroke. The clinical
manifestations of hyperactivity of sympathetic nerve after stroke are
possibly a reflection of the relative increase of sympathetic
activity caused by more decline of vagal activity. Both DC and
AC were correlated negatively with the severity of stroke. For
the protective effect of vagal nerve, a decline of vagal
modulation might have some predictive values for unfavorable
outcomes after stroke. Further studies for the predictive value
of DC and AC for the prognosis of stroke are deserved.
The authors sincerely thank the participants of this study
for their cooperation. This study was supported by grants
from the Science and Technology Foundation of Shanghai
The authors report no conflicts of interest in this work.
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