DELAYED RECOVERY OF CARDIOVASCULAR AUTONOMIC

FUNCTION AFTER MITRAL VALVE SURGERY

Evidence for Direct Trauma?

R. Bauernschmitt

, B. Retzlaff

, N. Wessel

, H. Malberg

, G. Brockmann

C. Uhl

and R Lange

German Heart Center Munich,

University of Potsdam,

University of Karlsruhe

Keywords: Biosignal processing, Baroreflex response, surgery.

Abstract: Baroreflex Sensivity (BRS) and heart rate variability (HRV) have significant influence on the patients’

prognosis after cardiovascular events. The following study was performed to assess the differences in the

postoperative recovery of the autonomic regulation after mitral valve (MV) surgery and aortic valve (AV)

surgery with heart-lung machine. 43 consecutive male patients were enrolled in a prospective study; 26

underwent isolated aortic valve surgery and 17 isolated mitral valve surgery. Blood pressure, ECG and

respiratory rate were recorded the day before, 24h after surgery and one week after surgery. BRS was

calculated according to the Dual Sequence Method, time and frequency parameters of HRV were calculated

using standard methods. There were no major differences between the two groups in the preoperative

values. At 24 h a comparable depression of HRV and BRS in both groups was observed, while at 7 days

there was partial recovery in AV-patients, which was absent in MV-patients: p (AV vs. MV)<0,001. While

the response of the autonomic system to surgery is similar in AV- and MV-patients, there obviously is a

decreased ability to recover in MV-patients, probably attributing to traumatic lesions of the autonomic

nervous system by opening the atria. Ongoing research is required for further clarification of the

pathophysiology of this phenomenon and to establish strategies to restore autonomic function.

1 INTRODUCTION

The well-known depression of cardiovascular

autonomic function following cardiac surgery is

related to a variety of reasons like anaesthesia and

the use of the heart-lung-machine (Brown et al.,

2003), (Bauernschmitt et al., 2004). The role of

direct surgical trauma to the autonomic nerves (AN)

is still unclear. The following study was performed

comparing patients with isolated aortic valve

replacement (AV, the surgical trauma to AN is

considered to be low) or isolated mitral valve

surgery (MV, high surgical trauma to AN is

expected). With regard to the hypothesis that there is

a traumatic lesion of the cardiovascular autonomic

nervous system by opening the atria we observe the

postoperative recovery of AV- and MV-patients.

2 METHODS

43 consecutive male patients were analysed. 26 of

them underwent aortic valve surgery and 17 of them

mitral valve surgery. The mean age of AV-patients

was 63 +/- 13 years and the mean age of MV-

patients 59 +/- 12 years. Patients with concomitant

coronary heart disease were excluded for the known

effects of atherosclerosis. Perioperative medication

was standardized.

Anaesthesia was standardized; induction was

performed with sufentanil and midazolam. For

maintaining narcosis, a continuous infusion of

propofol was given; muscle relaxation was achieved

by pancuronium. Central venous pressure and

pulmonary artery pressure were monitored by a

Swan-Ganz catheter, arterial pressure by cannulation

of the radial artery. All operations were carried out

with cardiopulmonary bypass (CPB) in mild

hypothermia (32-34°C) and pulsatile perfusion

mode, cold crystalloid cardioplegia or blood

cardioplegia (isolated bypass surgery) was used for

cardiac arrest. After declamping, most of the patients

needed one countershock to terminate ventricular

fibrillation.

After 10-min equilibrations to the environment,

non-invasive blood pressure signals were collected

504

Bauernschmitt R., Retzlaff B., Wessel N., Malberg H., Brockmann G., Uhl C. and Lange R. (2008).

DELAYED RECOVERY OF CARDIOVASCULAR AUTONOMIC FUNCTION AFTER MITRAL VALVE SURGERY - Evidence for Direct Trauma?.

In Proceedings of the First International Conference on Bio-inspired Systems and Signal Processing, pages 504-507

DOI: 10.5220/0001064705040507

 SciTePress

from the radial artery by a tonometer (Colin Medical

Instruments) at 1000 Hz. Data were channelled into

a bed-side laptop after A/D-conversion and stored

for analysis. Simultaneously, breathing excursions

and a standard ECG were monitored. Data were

sampled for a 30-min period the day before surgery,

24h and seven days after surgery on the ICU. Care

was taken to perform the measurements during the

same time of the day in each patient. From the

recorded data the beat-to-beat intervals as well as the

beat-to-beat systolic and diastolic values were

extracted; premature beats, artifacts and noise were

excluded using an adaptive filter considering the

instantaneous variability.

Baroreflex Sensitivity (BRS): Dual Sequence

Method (DSM).

Using the DSM, the most relevant

parameters for estimating the spontaneous baroreflex

(BR) are the slopes as a measure of sensitivity. The

DSM is based on standard sequence methods with

several modifications: Two kinds of BBI responses

were analyzed: bradycardic (an increase in systolic

blood pressure (SBP)) that causes an increase in the

following beat-to-beat-intervals (BBI) and

tachycardic fluctuations (a decrease in SBP causes a

decrease in BBI). Both types of fluctuations were

analyzed both in a synchronous and in a 3-interbeat-

shifted mode. The bradycardic fluctuations primarily

represent the vagal spontaneous BR analysis of the

tachycardic fluctuations represent the delayed

responses of heart rate (shift 3) assigned to the

beginning slower sympathetic regulation. The

following parameter groups are calculated by DSM:

(1) the total numbers of slopes in different sectors

within 30 min; (2) the percentage of the slopes in

relation to the total number of slopes in the different

sectors; (3) the numbers of bradycardic and

tachycardic slopes; (4) the shift operation from the

first (sync mode) to the third (shift 3 mode)

heartbeat triple; and (5) the average slopes of all

fluctuations. DSM parameters are defined as

described by Malberg et al (European Heart Journal,

1996).

Heart rate Variability (HRV).

Respecting the

suggestions by the Task Force HRV (Malberg et al.,

2003), the following standard parameters are

calculated from the time series: MeanNN (mean

value of normal beat-to-beat intervals): Is inversely

related to mean heart rate. sdNN (standard deviation

of intervals between two normal R-peaks): Gives an

impression of the overall circulatory variability.

Rmssd (root mean square of successive RR-

intervals):

600

650

700

750

800

850

85 105 125 145

SBP [mmHg]

RRI [ms]

Avera

Slope

s>20

ms/m

mHg

Slope

Figure 1: Schematic representation of the two main

baroreflex parameters estimated by the Dual Sequence

Method: the average slope (dotted line) of all baroreflex

sequences as well as the total number of baroreflex slopes

above 20 ms/mmHg (thick lines). The thin lines symbolize

all baroreflex slopes below 20 ms/mmHg.

Higher values indicate higher vagal activity.

Shannon (the Shannon entropy of the histogram):

Quantification of RR-interval distribution. Apart

from the time-domain parameters mentioned above,

the HRV analysis focused on high-frequency

components (HF, 0.15-0.4 Hz, high values indicate

vagal activity) and low-frequency components (LF,

0.04-0.15 Hz, high values indicate sympathetic

activity). The following ratios were considered: LFn

– the normalized low frequency (LFn=LF/(LF+HF)),

HP/P - the to the total power P normalized high

frequency as well as LP/P - the P-normalized low

frequency.

Nonlinear Dynamics.

New parameters can be

derived from methods of nonlinear dynamics, which

describe complex processes and their interrelations.

These methods provide additional information about

the state and temporal changes in the autonomic

tonus. Several new measures of non-linear dynamics

in order to distinguish different types of heart rate

dynamics as proposed by Kurths were used. The

concept of symbolic dynamics is based on a coarse-

graining of dynamics. The difference between the

current value (BBI or systolic blood pressure) and

the mean value of the whole series is transformed

into an alphabet of four symbols (0; 1; 2; 3).

Symbols '0' and '2' reflect low deviation (decrease or

increase) from mean value, whereas '1' and '3' reflect

a stronger deviation (decrease or increase over a

predefined limit, for details see Voss et al.

Subsequently, the symbol string is transformed to

'words' of three successive symbols explaining the

nonlinear properties and thus the complexity of the

system.

DELAYED RECOVERY OF CARDIOVASCULAR AUTONOMIC FUNCTION AFTER MITRAL VALVE SURGERY -

Evidence for Direct Trauma?

505

The Renyi entropy calculated from the distributions

of words ('fwrenyi025' - a = 0.25) is a suitable

measure for the complexity in the time series ('a'

represents a threshold parameter). Higher values of

entropy refers to higher complexity in the

corresponding time series and lower values to lower

ones. A high percentage of words consisting only of

the symbols '0' and '2' ('wpsum02') reflects

decreased HRV. The parameter 'Forbidden words

(FW)' reflects the number of words which never or

very rarely occur. A high number of forbidden

words are typical for regular behaviour, while in

highly complex time series, only very few forbidden

words are found.

3 RESULTS

There were no major differences among the two

groups preoperatively. At 24h after surgery, both

groups showed a comparable depression of HRV

and BRS. One week after surgery, however, marked

differences were present: SDNN 15+/-6 (MV) vs.

42+/-33 (AV); p<0.001 (Fig. 1).

HRV-sdNN

100

preoperative postoperative after 24h postoperative after 1

week

Figure 2: HRV-sdNN, heart rate variability - standard

deviation of beat to beat intervals.

HRV-HF

0,0

0,2

0,4

0,6

0,8

1,0

1,2

preoperative postoperative after 24h postoperative after 1

week

Figure 3: HRV-HF: heart rate variability – high frequency

(indicator for parasympathetic regulation).

Similar kinetics were found for the High- and

Low-Frequency components of HRV (HF 0.01+/-

0.02 (MV) vs. 0.38+/- 0.64 (AV); p<0.02 (Fig. 2, 3).

HRV-LF

0,0

0,2

0,4

0,6

0,8

1,0

1,2

1,4

1,6

1,8

preoperative postoperative after 24h postoperative after 1

week

Figure 4: HRV, low-frequency.

Regarding the nonlinear parameters, there was a

significant depression present already 24h after

surgery with mitral patients more suppressed than

aortic patients, these alterations being even more

distinct after one week (Fig. 4).

HRV-shannon entropy

0,0

0,5

1,0

1,5

2,0

2,5

3,0

preoperative postoperative after 24h postoperative after 1

week

Figure 5: HRV, Shannon-entropy.

The baroreflex was impacted in a similar way for

both the number and strength of regulations (BRS

bradycardic 4.5+/-1.2 (MV) vs. 7.3+/-2.7 (AV);

p<0.001 (Fig. 5, 6).

Baroreflex (brady, strength)

preoperat ive post operat ive

af t er 24h

post operat ive

af t er 1 week

Figure 6: BRS, strength of bradycardic regulations.

BIOSIGNALS 2008 - International Conference on Bio-inspired Systems and Signal Processing

506

number of regulations (bradycardic)

preoperative postoperative after 24h postoperative after 1

week

Figure 7: BRS, number of bradycardic regulations.

For the tachcardic part of the baroreflex, however,

the differences among aortic and mitral patients

failed significance after one week (p<0.08, data not

shown).

4 DISCUSSION AND

CONCLUSIONS

The last decade witnessed a strong increase in basic

knowledge of the cardiovascular autonomic system.

However, as far as alterations in the cardiac patient

and in patients undergoing open heart surgery are

concerned, we are still at the very start.

Meanwhile it is well known, that cardiac surgery

leads to an early depression of autonomic function,

and that there is potential for recovery after a certain

time frame. The mechanisms for both phenomena

are quite unclear, so the aim of the present study was

to shed light on the precise role of direct surgical

trauma. In contrast to earlier studies, where different

preoperative conditions and different surgical

procedures were mixed up, we focussed on patients

with isolated aortic valve disease and isolated mitral

valve disease, thus excluding the well known

influences of atherosclerosis on cardiovascular

autonomic function. On the other hand, the operative

procedures done in these patients offer two entirely

distinct entities of surgical trauma: while for aortic

valve replacement the heart is left more or less

untouched and the valve is approached by an

incision in the anterior aspect of the ascending aorta

only, in mitral valve operations, both the caval veins

are extensively dissected, and the heart is opened by

an incision right posterior to the interatrial groove,

where an abundance of autonomic nerve endings are

supposed to be.

The similar depression in both groups observed

at 24h may reflect the effects of standardized

anesthesia and perioperative treatment being

comparable in all patients. While AV-patients

showed a clear tendency to recover after one week,

no recovery was recorded in MV-patients. In our

opinion, this is a strong indicator of higher surgical

trauma to AN, if the atria are dissected. Recovery of

autonomic fibres is possible, even in heart transplant

patients, as described earlier, so the next step will be

investigating time and frequency parameters and

baroreflex sensivity after six months to give

evidence of the hypothesis of direct surgical trauma.

Summarizing, we were able to demonstrate for

the first time, that direct surgical trauma can be one

of the major mechanisms leading to depression of

cardiovascular autonomic function. The diversity of

results in earlier studies may be caused by the case-

mix of patients, comprising different initial

conditions as well as different extents of trauma.

ACKNOWLEDGEMENTS

This study was supported by grants from the

Deutsche Forschungsgemeinschaft (DFG BA

1581/4-1, BR 1303/8-1, KU 837/20-1).

REFERENCES

Brown CA, Wolfe LA, Hains S, Ropchan G, Parlow J.

Spontaneous baroreflex sensitivity after coronary

artery bypass graft surgery as a function of gender and

age. Can. J. Physiol. Pharmacol. 2003;(9): 894–902.

Bauernschmitt R, Malberg H, Wessel N, Kopp B,

Schirmbeck EU, Lange R. Impairment of

cardiovascular autonomic control in patients early

after cardiac surgery. Eur J Cardiothorac Surg 2004;

25(3):320-326.

Heart rate variability Standards of measurement,

physiological interpretation, and clinical use. Task

Force of The European Society of Cardiology and The

North American Society of Pacing and

Electrophysiology. European Heart Journal 1996; 17:

354–381.

Malberg H, Bauernschmitt R, Meyerfeldt U, Schirdewan,

A, Wessel N. Short-term heart rate turbulence analysis

versus variability and baroreceptor sensitivity in

patients with dilated cardiomyopathy. Z Kardiol 2003;

92(7):547-557.

DELAYED RECOVERY OF CARDIOVASCULAR AUTONOMIC FUNCTION AFTER MITRAL VALVE SURGERY -

Evidence for Direct Trauma?

507