Interact CardioVasc Thorac Surg 2009;8:426-430. doi:10.1510/icvts.2008.198747
© 2009 European Association of Cardio-Thoracic Surgery
Institutional report - Cardiac general |
Arterial baroreflex dysfunction after coronary artery bypass grafting
Mats Johanssona,b,*,
Ann-Kristin Karlssona,
Anna Myredala and
Evy Lidellc
a Department of Internal Medicine, Varberg Hospital, SE 432 81 Varberg, Sweden
b Department Clinical Physiology, Sahlgrenska University Hospital, Göteborg, Sweden
c School of Social and Health Sciences, Halmstad University, Halmstad, Sweden
Received 17 November 2008;
received in revised form 18 December 2008;
accepted 20 December 2008
 This work was supported by grants of US $20,000 from the Scientific Council of Halland and Sahlgrenska University Hospital.
*Corresponding author. Tel.: +46 340-481000; fax: +46 340-17343.
E-mail address: matsjohans{at}telia.com, mats.johansson{at}lthalland.se (M. Johansson).
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Abstract
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Although uncommon, the incidence of ventricular arrhythmia is high in certain subsets of patients after coronary artery bypass grafting. Arterial baroreflex dysfunction has been linked to increased risk of ventricular arrhythmia and sudden cardiac death. The aim of the current study was to explore arterial baroreflex function during the early recovery phase and up to five months after surgery. Electrocardiogram and beat-to-beat blood pressures were registered in patients (n=92) undergoing coronary artery bypass grafting five weeks and five months after surgery. Healthy subjects (n=31) were examined for comparison. The arterial baroreflex sensitivity and the baroreflex effectiveness index were calculated. The baroreflex sensitivity and the baroreflex effectiveness index were reduced by 36% and 64%, respectively (P<0.01 for both) in patients five weeks after coronary artery bypass grafting compared to healthy subjects (HS). Values increased during follow-up but the baroreflex effectiveness index remained reduced by 55% in patients compared to HS five months after cardiac surgery (P<0.01). Arterial baroreflex dysfunction prevails both early and long-term after coronary artery bypass grafting. Reduced modulation of cardiac parasympathetic nervous activity could contribute to the increased risk of ventricular arrhythmia observed during the early recovery phase after cardiac surgery.
Key Words: CABG; Arterial baroreflex function
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1. Introduction
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Sustained ventricular tachycardia in the recovery period after coronary artery bypass grafting (CABG) is uncommon but the incidence is high in patients with previous myocardial infarctions, congestive heart failure and low left ventricular ejection fractions [1]. Given the high mortality associated with sustained ventricular tachycardia after CABG, identifying high-risk individuals is of importance.
We have recently presented data suggesting elevated lability of cardiac repolarisation after coronary artery bypass grafting (CABG) which could increase the susceptibility for ventricular arrhythmia postoperatively [2]. The current paper presents the data regarding the arterial baroreflex function after CABG. Experimental data indicate that a preserved modulation of cardiac parasympathetic nervous activity could protect against ventricular arrhythmia [3]. Furthermore, the experimental data are supported by results from clinical studies of the arterial baroreflex sensitivity (BRS) [4]. Furthermore, we have previously reported that the baroreflex effectiveness index (BEI), which reflects the number of times the arterial baroreflex is being in controlling the heart rate response to blood pressure fluctuations, was an independent predictor of mortality in patients with chronic renal failure, whereas BRS was a predictor of sudden death [5]. Previous studies, comprehending rather small numbers of patients, have reported arterial baroreflex dysfunction during the early recovery phase after cardiac surgery compared to values obtained preoperatively [6–8]. Since there are few previous reports on the long-term modulation of cardiac parasympathetic nervous activity after CABG, the aim of the present study was to assess BRS and BEI during the early recovery phase and long-term after CABG surgery. These variables are of potential clinical interest given their relation to cardiovascular morbidity and mortality [4, 5].
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2. Patients
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2.1. Study population
Patients in the current study followed the ordinary rehabilitation program after CABG surgery and the investigations were performed at the scheduled visits at the hospital five weeks and five months after CABG surgery. For comparison, investigations were performed in healthy subjects (HS) of similar age and gender distribution as the patients.
The local ethical committee at Sahlgrenska University Hospital approved the study and all subjects gave their informed consent to participate.
2.2. CABG patients
All patients (n=157) who were referred to Varberg Hospital for rehabilitation after CABG surgery between January 2002 and October 2003 were invited to participate in the study. Fifteen patients refused to participate, 15 were excluded because of inability to speak Swedish and 35 were excluded because of atrial fibrillation which interfered with the BRS analyses. Hence, 92 patients (average age 64±9 years, range 41–75 years, 17 females) were included in the study and underwent investigations five weeks after CABG, whereas two patients refused to attend at the five-months visit and hence, ninety patients underwent both investigations. Two patients underwent re-operations because of bleeding, two were treated for postoperative pericarditis, one had pneumonia, one was treated for venous thrombosis and 11 patients had transient postoperative atrial fibrillation. Six patients underwent combined CABG and heart valve surgery. Forty-five percent were hypertensive or were on antihypertensive treatment, 56% had a history of previous myocardial infarction and 14% had diabetes.
2.3. Healthy subjects
Thirty-one healthy controls of similar age and gender distribution as the patients (average age 63±9 years, range 36–75 years, 6 females) were recruited from the staff at Sahlgrenska University Hospital or by advertisement in a local newspaper. All healthy subjects were non-smokers, had no significant past medical history and were not taking any regular medication. They were all normotensive with normal ECGs.
2.4. Experimental protocol
Patients were included in the study when they were awaiting CABG surgery or during the postoperative hospital stay. They all followed the ordinary rehabilitation program at the cardiology department of Varberg Hospital with one organized exercise session each week up to six months after surgery. The rehabilitation program was led by a team consisting of a rehabilitation nurse and a physiotherapist who collaborated with a social worker specialized in medical and health care. Patients were examined by a physician at five weeks and five months after surgery. All patients underwent echocardiography five months after surgery with measurements according to the American Society of Echocardiography [9]. Acuson Sequoia C512 ultrasound equipment was used for echocardiography. All investigations were performed by a specialist in cardiology who has 15 years experience of echocardiography. Images were stored on a hard disk and measurements were performed offline. The average of three measurements was used.
A clinical investigation by the responsible physician was performed at the visits and sphygmomanometer cuff blood pressures were measured by a nurse after 10 min rest in the supine position. ECG and beat-to-beat blood pressure were registered during 20 min supine rest.
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3. Methods
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3.1. Data acquisition and calculations
All subjects refrained from caffeine-containing beverages for at least 12 h before the investigations. Subjects rested supine in a quiet room for 10 min. After the resting period, simultaneous surface ECG (lead II) and beat-to-beat blood pressure signals (Portapres, TNO Biomedical Instrumentation, Amsterdam, The Netherlands) were acquired for 20 min. The accuracy of the Portapres device has been validated previously [10]. Registrations were recorded at a sampling frequency of 1000 Hz and stored on a personal computer. The recordings were inspected off-line for removal of artefactual segments and sequences containing non-sinus beats. Ectopic beats were corrected by interpolation.
The time series of SBP and pulse intervals (defined as the interval between the R-waves of two consecutive heart beats on the ECG) from the entire recording period were scanned to identify baroreflex sequences, which were defined as three or more consecutive beats in which successive SBP and pulse intervals concordantly increased or decreased, with the threshold set at 1.0 mmHg and 5.0 ms, respectively, and a shift of +1 between the blood pressure pulse and the pulse intervals [11].
Linear regression was applied to each sequence and only those with the squared correlation coefficient (r2) >0.85 were accepted for further analysis. The arterial baroreflex function was estimated by calculating: i) The spontaneous BRS, reflecting the average regression slope for all the linear regressions plotted for accepted baroreflex sequences within the whole time frame, ii) The numbers of sequences per 1000 heart beats, and iii) The baroreflex effectiveness index (BEI), defined as the ratio between the number of SBP ramps followed by the respective reflex pulse interval (PI) ramps that fulfilled the BRS criteria and the total number of SBP ramps during the recording period according to the equation [12]:
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For each blood pressure ramp the overall blood pressure change was calculated and the slope of the ramp was estimated by the maximum of the first derivative of the blood pressure signal within the time interval of the ramp (max dP/dt). Original data from two subjects are depicted in Fig. 1.
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Fig. 1. Figures are showing the individual regression lines fulfilling the baroreflex criteria defined in the Methodology section. The slope of the thick line in each figure represents the average slope of the individual regression lines and hence, the spontaneous BRS. The baroreflex effectiveness index (BEI) was defined as the ratio between the number of SBP ramps followed by the respective reflex pulse interval ramps that fulfilled the BRS criteria and the total number of SBP ramps during the recording period. To the left an example of a patient with reduced BRS and to the right a healthy subject with normal BRS is depicted.
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3.2. Statistics
Numerical distributions are presented by their mean±S.D. Student's t-test for unpaired and paired comparisons was used for continuous data with a normal distribution. BEI showed a non-normal distribution and hence, the Mann–Whitney U-test and Wilcoxon's signed-rank test for unpaired and paired comparisons were used. For comparisons of depression scale values, non-parametric tests were used. Comparisons of proportions were carried out using cross-tabulation and Fisher's exact test. For comparison of paired proportions, McNemar's test was used. The relationship between two variables was assessed from bivariate scatter plots and calculation of the rank correlation coefficient was performed according to Spearman. Statistical significance was defined as P<0.05.
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4. Results
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Patients who underwent CABG did not differ compared to HS regarding age or gender distribution but had elevated body mass index (BMI, P<0.01, Table 1) which remained unchanged during the follow-up. Although there was a decline in blood pressure between the 5-week and 5-month visits after CABG, blood pressures remained elevated among patients compared to HS (P<0.01, Table 1). Heart rate did not differ between patients and HS, either at the 5-week or 5-month visits but decreased among patients during the follow-up (P<0.01, Table 1). BRS and BEI were all reduced among patients compared to HS by 36% and 64%, respectively (P<0.01 for all, Table 1). Both BRS and BEI increased between the 5-week and 5-month visits (P<0.01, Table 1). BEI remained reduced by 55% compared to HS five months after surgery (P<0.01), whereas BRS did not differ. The overall pressure change of the SBP ramps that was followed by the respective reflex PI interval ramps that fulfilled the BRS criteria and the slope of the SBP ramps (max dP/dt) did not differ between patients and HS (5.9±1.6 mmHg and 2.7±0.7 mmHg/ms for patients vs. 5.7±2.2 mmHg and 3.0±1.5 mmHg/ms for HS) and these variables remained unchanged between five weeks and five months after CABG. The average LVEF five months after CABG was 57±9% (range 30–70%), 14% showed reduced left ventricular systolic function with LVEF <50%. Neither BRS nor BEI differed among patients having LVEF below 50% and other patients. Medical treatments are displayed in Table 2. There were no relationships between BRS or BEI and any of the medical treatments. Laboratory variables among patients five weeks and five months after CABG surgery are displayed in Table 3.
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Table 1 Demographical and hemodynamical variables in patients at 5 weeks and 5 months after CABG surgery and healthy subjects (HS)
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5. Discussion
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The current findings extend previous knowledge regarding arterial baroreflex function after CABG by comprehending a larger study population and by performing repeated measurements during follow-up. Furthermore, measurements of BEI, a novel index reflecting the number of times the arterial baroreflex is being active has not previously been reported after CABG. Hence, a reduced BEI up to five months after CABG surgery is a novel finding. This indicates that the arterial baroreflex is less effective in overcoming non-baroreflex influences on blood pressure and heart rate in patients who have undergone CABG surgery. In contrast to BRS, the impairment of BEI improved only slightly up to five months after surgery, suggesting that this aspect of the arterial baroreflex function remains impaired long-term after CABG.
Di Rienzo and co-workers reported that sino-aortic denervation in cats reduced BEI to a value near zero, supporting the contention that BEI was related to arterial baroreflex function [12]. The mechanisms responsible for the reduced BEI in patients who had undergone CABG are not obvious. A larger magnitude of the blood pressure changes of the individual ramps and/or steeper slopes of the blood pressure ramps have been associated with higher BEI values [12]. However, in the current study there were no differences between patients who had undergone CABG and healthy subjects regarding these variables and there was no change between the 5-week and 5-month investigations. In 216 hypertensive patients with chronic renal failure, diabetes (together with age) was an independent predictor of BEI, supporting neuropathy as a contributor to reduced BEI [13]. Hence, one may speculate that an intraoperative injury to the cardiac parasympathetic nerves could have contributed to the reduced BEI. The number of patients in the present study was too low to permit a multivariate analysis.
A reduced BRS has been linked to an adverse outcome after a myocardial infarction, stroke and in patients with chronic renal function [4, 5, 14]. There are, however, few reports on the arterial baroreflex function after CABG. Bauernschmitt and co-workers reported reduced BRS in 25 patients during the first 20 h after CABG whereas Brown et al. reported a decline in BRS five days postoperatively compared to preoperative measurements in 34 patients [6, 7]. These data indicate that the reduction of BRS during the early recovery phase after CABG, at least in part, is caused by the surgery. Moreover, physical inactivity after surgery could have contributed to the impaired arterial baroreflex function five weeks after surgery. This notion is supported by the findings of improved BRS in patients who underwent an exercise program during the first six weeks after CABG, whereas no significant change occurred in untrained individuals [15]. Moreover, patients with coronary disease have reduced arterial distensibility and one may speculate that larger blood pressure fluctuations were needed to activate the arterial baroreceptors and hence, reduced arterial distensibility could have contributed to the baroreflex dysfunction.
5.1. Study limitations
The present study is limited by the lack of preoperative investigations. Hence, it is likely that some of the observed differences regarding arterial baroreflex function compared to HS would have prevailed preoperatively. However, previous data suggest a reduction of BRS after cardiac surgery when investigations before surgery were compared to those performed early afterwards [6, 7]. Moreover, improved BRS and BEI five months after surgery compared to values obtained five weeks postoperatively suggest that CABG and not only atherosclerotic vascular disease per se contributes to the arterial baroreflex dysfunction observed. Although there were no differences in BRS or BEI among patients on or off treatment with beta blockers, ACE inhibitors, angiotensin receptor blockers or diuretics, the groups were too small to rule out drug effects. Elevated BMI and systolic blood pressures among patients compared to healthy subjects could explain some of the differences in BRS and BEI observed.
In summary, reduced modulation of cardiac parasympathetic nervous activity after CABG, the present study indicates that baroreflex dysfunction prevails long-term during the recovery phase after CABG surgery. Whether arterial baroreflex dysfunction may contribute to the increased susceptibility for ventricular arrhythmia observed in subsets of patients during the early recovery phase after CABG remains to be elucidated in future studies.
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Acknowledgements
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We gratefully acknowledge Folke Karlsson for building and supporting the database and Gun Bodehed-Berg, Anette Fajerson, Ann-Lis Wänman, Annika Stener-Bengtsson and Ruth Jonsson for excellent technical assistance when performing the investigations.
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Abstract
1. Introduction
