Correlation of Chronotropic Index and Heart Rate
Recovery to Heart Rate Variability and Diastolic Function Values in
M. Tolga Dogru, Serdar Gunaydin, Vedat Simsek, Murat Tulmac, Mahmut
Guneri: Correlation of Chronotropic Index and Heart Rate Recovery to
Heart Rate Variability and Diastolic Function Values in Men. The
Internet Journal of Cardiology. 2007. Volume 4 Number 2.
between heart rate recovery (HRR), chronotropic index (CI) values
and autonomic and diastolic function data has importance in
predicting the pathologic states that coincide with each other in
clinical assessment. The aim of the study is to show the
relationship of autonomic system and HRR, CI and diastolic
functions of the heart.
Method: Fifty-eight healthy
asymptomatic men were included in the study. History, physical
examination, routine biochemistry, ECG, 24-hour Holter monitoring,
color Doppler echocardiography, tissue Doppler echocardiography
and exercise stress test were applied to all
While there was a positive correlation between HRR values and
logarithmic low frequency (LogLF) and high frequency (LogHF)
values (p=.010, p=0.002 respectively); there was a negative
correlation with Log LF/LogHF (p=0.034). Comparison of groups
having CI below and over 0.8 showed that E/A ratio of transmitral
flow was high in low CI subjects (p=0.035,Z : 2109)
Conclusion: HRR and CI showed strong positive
correlation with parasympathetic tone as well as diastolic
Men are in a higher risk group than women for having hypertension
3 , coronary artery disease
3 , stroke
3 , sudden cardiac death
Higher sympathetic tone in men particularly before 60 years of age
than women 5 ,
6 may increase cardiovascular
morbidity and mortality 7 . Heart rate recovery (HRR) and
chronotropic index (CI) values have been shown to predict cardiovascular
morbidity and mortality 7 ,
26 . Thereby, showing
the effects of autonomic balance that could be determinative for
replying inner or outer stress factors, on HRR, CI and diastolic
functions of the heart is valuable for addressing of autonomic effects
on cardiac morbidity and mortality. This study aims at assessing the
relationship between HRR, CI, diastolic functions and demonstrating how
changes on autonomic balance could affect these factors in the group of
healthy asymptomatic men
Patients And Methods
Following ethical approval of institutional board and obtaining
informed consent, fifty-eight healthy asymptomatic men. Age, height,
weight, body mass index, waist and hip circumference, waist/hip ratio
were recorded. History, physical examination, routine biochemical tests,
complete blood count, thyroid function tests, 12 lead ECG and 24 hour
Holter examination (Delmar –Impresario, General Electric, USA) were
obtained. Chest X-ray, color Doppler echocardiography (GE-Vivid 7 Pro,
General Electric, Florida-USA) and exercise stress test (Quinton 4500
treadmill, Seattle, ABD) were applied to the subjects for differential
diagnosis when required. All the tests for each were completed in 15
24 Hour Holter Monitoring, Heart Rate Variability
Heart rate variability measurements are examined from the records
that have no artifacts. Fast Fourier transformation system is used for
the evaluation of heart rate variability.
The following parameters were measured:
LF: (Low Frequency) (0.04-0.15 Hz) (msn2): LF band
reflects both sympathetic and parasympathetic activity and is associated
with baroreflex activity.
HF: (High Frequency) (0.15-0.4 Hz.) (msn2): HF band is
associated with respiratory frequency and respiration related heart rate
changes (respiratory sinus arrhythmia) and reflects cardiac vagal
LF/HF: LF/HF ratio is believed to reflect sympathetic/parasympathetic
activity ratio by some authors.
Normalized LF (LFn ): [LF/(LF+HF) ] ratio
Normalized HF (HFn ) : [HF/(LF+HF) ] ratio
Normalized LF (LFn ) and Normalized HF (HFn )
Normalized LF and normalized HF are the percentage of each parameter
to total power.
Total power (msn
): It is the total band
width consisting of VLF,LF,HF and VHF. 8
pNN50 (%): percent of differences between adjacent normal RR
intervals that are greater than 50 ms over the entire 24 hour
RMSSD (root mean square of successive differences): the square root
of the mean of the squared differences between adjacent normal RR
intervals over the entire 24 hour recording. It is an important marker
of parasympathetic activity. 8 .
As the results are more valuable logarithmic transformations of LF,
HF and LF/HF values are also used in the study
Transthoracic Color Doppler Echocardiography
Transthoracic color Doppler echocardiography was done to all of the
participants included in the study. Transmitral Doppler flow
measurements are taken from the tips of the mitral valve leaflets in
apical four chamber view if the patient has normal chamber sizes, no
morphologic abnormality, segmental wall motion disorder, hypertrophy or
dilatation. E wave velocity, A wave velocity, E/A ratio, mitral E wave
deceleration time, isovolumic relaxation time(IVRT), isovolumic
contraction time (IVCT), mitral flow period (the period from the
beginning of E wave to end of A wave), diastolic period (IVRT +
Diastolic filling period :DFP), were measured.
By using tissue Doppler echocardiography Ea, Aa and Ea/Aa ratios were
measured. Mainly we used the criteria for evaluation and definition of
vary types of diastolic dysfunction that shown in table 6.
, 10 ,
11 Additionally E/Ea ratio which gives an
idea about left ventricular filling pressure is measured and the
correlation between other variables is determined
Table 6: Definitions of some data used in article and
diastolic dysfunction criteria
Exercise Stress Test
All of the participants were tested using Bruce Protocol between
14:00 and 16:00 in daytime. A light lunch and a 30 minute rest were
applied. In the case of excessive tea ,alcohol, and coffee intake and
excessive physical activity the test was delayed. Getting target heart
rate, symptoms about angina or equivalents, ischemic
electrocardiographic changes during the test are accepted as positive
and the participant's request were indications to terminate the test
12 .After terminating the test, heart rate was recorded in
the cool down period's first and third minutes
Heart Rate Recovery (HRR) was calculated as [HRR= HRpeak –
HR 1.minute rest ].
Chronotropic index (CI) was calculated as [(HRpeak
–HRrest)/ (220– age– HRrest)]
The participants were grouped according to HRR value's being below 12
and above 12, chronotropic index being below 0.8 and above 0.8. and the
differences between these groups were examined.
SPSS 11.5 for Windows was used for statistical analysis. The
correlation between the data were analyzed by Pearson and Spearman
tests. The factors to have an influence on results like age, weight,
body mass index, waist circumference hip circumference and waist/hip
ratio were controlled by 2 way partial correlation. Partial correlation
analysis results are shown in tables. Mann-Whitney U test was used for
the comparisons of CI data as the data were not normally distributed.
The results were shown in tables as mean± Standard deviation (SD) and Z
values. P value less than 0.05 was defined as statistically
Table 1 demonstrates the baseline data of all the participants. In
the tables about correlation data, the partial correlation analysis
results are shown in order to eliminate the possible effects of age,
weight, body mass index, and waist/hip ratio. The positive and negative
signs shown before the p values points out the direction of the
Table 1: Patient characteristics
Table 2 reveals the HRR and chronotropic index data obtained after
exercise stress testing and heart rate variability data. HRR was
negatively correlated both minimal and mean heart rate that determined
24 hour holter monitoring (p=0.028 and p=0.002 respectively). Otherwise
HRR was positively correlated with both the HRR parameters Log LF and
Log HF(p=0.01 and p=0.002 respectively) and time based parameters pNN50
and RMSSD(p=0.022 and p=0.032 respectively).HRR was negatively
correlated with as a sympathetic tone marker LogLF/LogHF ratio (p=0.034
and p=0.028 respectively)
Table 2: Heart rate variability data, HRR and CI
Table 2 shows the partial correlations between HRR,CI and HRR.
Chronotropic index was also positively correlated with LogLF
(P=0.019).Both HRR and CI was positively correlated with total power
(p=0.013 and p=0.006 respectively)
Although not being the main purpose of our study HRR data were
compared with transmitral flow patterns and tissue Doppler data (Table
3).While autonomic tone values were not correlated with transmitral flow
patterns, there was a close correlation with tissue Doppler data. As a
sympathetic tone marker, LFn were negatively correlated with Ea and
Ea/Aa (p<0.001 and p=0.001 respectively) whereas positively
correlated with E/Ea (p=0.037)which is suggested to be positively
correlated with diastolic filling pressure( 9 ,
, 11 ).These correlations were exactly the opposite for the
parasympathetic tone marker HFn (table 3). As a symphatetic tone marker,
LFn/ HFn mainly correlated same way by LFn with echocardiographic data.
LFn/ HFn was negatively correlated with Ea and Ea/Aa (p<0.001 and
p<0.001 respectively); positively correlated with E/Ea (p=0.004)
Table 3: The correlations between transmitral and tissue
Doppler data and some significant heart rate variability
HRR and CI were significantly correlated with echocardiographic and
HRR,CI and diastolic function relations were also examined in our
study.(Table 4 )which shows the partial correlation results demonstrates
the parasympathetic tone marker HRR( 7 ) was positively
correlated with diastolic period and mitral flow period and negatively
correlated with systolic/diastolic period(p=0.002,p=0.025 and p=0.005
respectively). HRR and CI likewise heart rate variability measures were
not correlated with transmitral flow patterns (only E/A ratio is
correlated with HRR. p=0.048) but correlated with tissue Doppler data.
HRR was positively correlated with Ea and Ea/Aa (p=0.050 and p=0.001
respectively) whereas negatively correlated with Aa and E/Ea (p=0.012
and p=0.024 respectively).But the correlation between CI and tissue
Doppler data was more significant. CI was positively correlated with Ea
and Ea/Aa (p=0.002 and p=0.001 respectively) and negatively correlated
with E/Ea (p<0.001)
Table 4: Echocardiographic data, HRR and CI
After performing the exercise stress test the chronotropic indexes
were calculated and the participants were divided into two subgroups
according to having a CI value of less than or equal to 0.8 or above
0.8. Comparisons about these two subgroups are shown in table 5. As only
4 of 58 participants had the pathologic value of less than 12/minute
subgroup analysis was not done. The subgroup having a CI index of less
than 0.8 has decreased HF(parasympathetic tone) , total power and SDNN
(p=0.023, Z:2.271; p=0.013, Z:2.471; P=0.042, Z: 2.035 respectively),
and increased transmitral E/A ratio and E/Ea (p=0.035 Z:2.109;
p<0.001 Z:4.625 respectively) decreased Ea wave and Ea/Aa (p<0.001
Z:3.646 ; p<0.001 Z:3.835 respectively)
Table 5: Echocardiographic and heart rate variability data
with respect to chronotropic index
HRR and chronotropic index both as an autonomic tone marker and
having prognostic significance has been the subject of many studies
recently 7 .Previous studies have shown that HRR is a good
marker of parasympathetic activity 7 ,
14 . The close relation between HRR and heart rate
variability and the parasympathetic tonus marker HF is well documented
15 .Our study stated a significant positive
correlation between HRR and all the parameters of parasympathetic tone
.The correlation between HF and HRR was present also after eliminating
the effect of age, weight, waist and hip circumferences (table 2 ).
Not only the HF parameter but also the LF values were positively
correlated with HRR. LF value generally defined as a sympathetic tonus
marker 8 ,
17 is thought to be
related with both sympathetic and parasympathetic tonus, sympathetic and
parasympathetic efferent modulation of baroreflex activity, sympathetic
modulation of vasomotor activity and increases during the reflex
activities with the changes in blood pressure
19 . There
are studies that LF component is not solely related with sympathetic
activity 19 ,
28 .Previous studies has not
examined the relation of HRR and LF values in detail. The significant
negative correlation between LF and HRR determined by Evrengul et al
21 was not noted in our study. But contrarily to our study
that study was executed on a population of coronary artery disease. HRR
which is an important marker of parasympathetic activity
not only had positive correlation with parasympathetic tonus parameters
but also with the LF values indicating that the vagal control mechanism
is not free from LF value. Martinmaki et al stated decrement of LF and
total power besides the HF value after complete vagal blockade
22 .LF value is believed to reflect not only sympathetic but
also the parasympathetic activity 7 ,
22 . These results can explain the correlation between HRR
and LF values found in our study. The sympathovagal balance marker LF/HF
showed a strong negative correlation with HRR as usual. The increase in
sympathetic tone results in shortening of the sinoatrial node recovery
time. In addition to these HRR is positively correlated with SDNN values
which have predictive value for cardiovascular mortality
As the predictive value of HRR for cardiovascular morbidity has already
been known, it is not surprising for HRR to be correlated with other
There was a significant correlation between HRR and diastolic
function data. Autonomic system is suggested to be the factor that
relates this group of data. The presence of positive correlation with Ea
and Ea/Aa and the negative correlation with E/Ea with both HRR and CI
suggested that the increase in sympathetic tonus shows the same effect
on ventricular muscle and sinus node. Previous studies have emphasized
on the close relationship between tissue Doppler data and autonomic
tonus. 23 .Obtained data suggested that the increase in
sympathetic tonus decreased the compliance of ventricular myocardium
besides decreasing HRR and CI by the effect on sinus node. While there
was not a significant correlation between HRR and transmitral flow
values, there was a significant correlation between HRR and tissue
Doppler data. This may be related to the fact that transmitral flow is
highly dependent on other factors affecting volume and transmitral flow
10 .This study also revealed the significant correlation
between tissue Doppler data and autonomic tonus. A decrease in Ea wave
and an increase in Aa wave is seen with the increase in sympathetic
tonus while the increase in parasympathetic tonus is correlated with the
increase in Ea wave. This situation can be explained with the increased
sympathetic tone but it is surprising to see this finding in
asymptomatic men. This demonstrates that the decrease in ventricular
compliance due to sympathetic tonus does not have to occur in a
pathologic state. The correlation between the diastolic functions
obtained by tissue Doppler and heart rate variability has been
demonstrated in previous studies, but this is beyond our study purpose.
The strong correlation between HRR and diastolic period that is affected
by parasympathetic tonus is an expected result. As it is known, E/Ea is
correlated with left ventricular filling pressure.
11 HRR is negatively correlated E/Ea in our study. The
increase in sympathetic tonus increases left ventricular filling
pressure besides decreasing HRR.
Chronotropic index also predicts cardiovascular morbidity and
mortality like HRR 20 ,
22 . CI
was positively correlated with LF like HRR. But the insufficiency of the
chronotropic adaptability can not be explained with the presence of the
parasympathetic component of LF. This partially contrary state may be
related with the positive correlation of LF seen with adrenalin but not
with noradrenalin 28 .Colucci et al. stated desensitization
to noradrenalin after a long term sympathetic activation
.The desensitization formed against beta1 receptors can be bypassed with
adrenalin which also stimulates beta2 receptors. The effect of beta2
receptors on the control of heart rate has been documented
. Adrenalin is thought to control the heart rate by beta2 receptor
stimulation when noradrenalin increase in response to exercise
30 has less effect on heart rate control due
to down- regulated beta1 receptors under chronic stimulation
29 . Adrenalin forms the escape pathway of
chronotropic response by the help of desensitized beta2 receptors
31 .At this point of view,
the positive correlation of LF value with increased adrenalin and
chronotropic index is an expected result. But the study design and the
results are not sufficient to comment. Further studies with larger group
of subjects are warranted.
The autonomic tonus changes that explains the relation between HRR
and tissue Doppler data is also responsible for the same relation
between CI and tissue Doppler data. The comparison of the two subgroups
of CI grouped according to having values less or equal to 0.8 or greater
than 0.8, supports our other results.
The decrease in Ea/Aa ratio which is a marker of the decrease in CI
and ventricular compliance and the increase in E/Ea ratio which is
related with increased ventricular filling pressure are the results of
possible increased sympathetic tonus particularly under the effect of
noradrenalin. Although not being tested noradrenalin levels are expected
to be high in the group of low CI values 7 ,
. Another interesting result that took attention, contradictory negative
correlation was determined transmitral flow E/A ratio and CI. It was
interpreted that this result depended on flow dependency of transmitral
echocardiographic values. Also it was considered us, increased end
diastolic pressure of left ventricle and more restrictive response
accompanied increased sympathetic tone even though the group is healthy.
HRR and chronotropic index values which have important predictive
value for cardiac morbidity and mortality are associated with the
changes in sympathetic tonus and these changes parallels with the
diastolic function changes.
Address for Correspondence
Dr. M .Tolga DOGRU,
University of Kirkkale, Kirikkale-Turkey
Tel:+90-3182252485 , +90-5554727096
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