http://informahealthcare.com/dre ISSN 0963-8288 print/ISSN 1464-5165 online Disabil Rehabil, Early Online: 1–8 ! 2013 Informa UK Ltd. DOI: 10.3109/09638288.2013.782362
RESEARCH ARTICLE
Renata Gonc¸alves Mendes1, Rodrigo Polaquini Simo˜es1, Fernando de Souza Melo Costa1, Camila Bianca Falasco Pantoni1, Luciana Di Thommazo-Luporini1, Se´rgio Luzzi2, Othon Amaral-Neto2, Ross Arena3, Aparecida Maria Catai1, and Audrey Borghi-Silva1 1
Cardiopulmonary Physiotherapy Laboratory, Nucleus of Research in Physical Exercise, Federal University of Sao Carlos, Sao Paulo, Brazil, Irmandade Santa Casa Misericordia Hospital, Araraquara, Sao Paulo, Brazil, and 3Department of Physical Therapy, College of Applied Health Sciences, University of Illinois Chicago, Chicago, IL, USA
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Abstract
Keywords
Purpose: To assess whether the same exercise-based inpatient program applied to patients with normal and reduced left ventricular function (LVF) evokes a similar cardiac autonomic response after coronary artery bypass graft (CABG). Method: Forty-four patients post-CABG, subgrouped according to normal LVF [LVFN: n ¼ 23; left ventricular ejection fraction (LVEF) 55%] and reduced LVF (LVFR: n ¼ 21; LVEF 35–54%), were included. All initiated the exercise protocol on post-operative day 1 (PO1), following a whole progressive program until discharge. Cardiac autonomic response was assessed by the indices of heart rate variability (HRV) at rest and during exercise (extremity range of motion and ambulation). Results: During ambulation, lower values of HRV indices were found in the LVFR group compared with the LVFN group [standard deviation of all RR (STDRR; 6.1 2.7 versus 8.9 4.7 ms), baseline width of the RR histogram (TINN; 30.6 14.8 versus 45.8 24.9 ms), SD2 (14.8 8.0 versus 21.3 9.0 ms), Shannon entropy (3.6 0.5 versus 3.9 0.4) and correlation dimension (0.08 0.2 versus 0.2 0.2)]. Also, when comparing the ambulation to rest change, lower values were observed in the LVFR group for linear (STDRR, TINN, RR TRI, rMSSD) and non-linear (SD2 and correlation dimension) HRV indices (p50.05). On PO1, we observed only intra-group differences between rest and exercise (extremity range of motion), for mean intervals between heart beats and heart rate. Conclusion: For patients with LVFN, the same inpatient exercise protocol triggered a more attenuated autonomic response compared with patients with LVFR. These findings have implications as to how exercise should be prescribed according to LVF in the early stages following recovery from CABG.
Autonomic nervous system, coronary artery bypass graft, myocardial function, physical therapy
ä Implications for Rehabilitation
Exercise-based inpatient program, performed by post-CABG patients who have normal left ventricular function, triggered a more attenuated cardiac autonomic response compared with patients with reduced left ventricular function. Volume of the inpatient exercises should be prescribed according to the left ventricular function in the early stages following recovery from CABG.
History Received 30 September 2012 Revised 25 February 2013 Accepted 1 March 2013 Published online 7 May 2013
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Is applying the same exercise-based inpatient program to normal and reduced left ventricular function patients the best strategy after coronary surgery? A focus on autonomic cardiac response
Introduction The transition from rest to exercise requires rapid adjustments by the cardiovascular system to meet increased demand, which is mainly mediated by the autonomic nervous system [1,2].
Address for correspondence: Renata Gonc¸ alves Mendes, PhD, Cardiopulmonary Physiotherapy Laboratory, Federal University of Sao Carlos-Sao Paulo-Brazil, Rod. Washington Luis KM 235 CEP, 13565-905 Sa˜o Carlos, Brazil. Tel: +55 16 33518952. Fax: +55 16 33612081. E-mail:
[email protected]
Moreover, it has been suggested that there is impairment of cardiac autonomic regulation in patients who have undergone coronary artery bypass grafting (CABG) [3–6]. Heart rate variability (HRV) represents the method widely used to assess cardiac autonomic nervous activity non-invasively and deleterious alterations in these measurements are common acutely following CABG [5,7]. In this context, impairment of cardiovascular autonomic regulation has been associated with increased risk of cardiovascular mortality and morbidity [8,9], and more specifically in these patients, the higher occurrence of myocardial ischemia and prolonged hospital stay following the surgical procedure [6,10].
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The early implementation of cardiac rehabilitation, including a physical exercise component, has resulted in beneficial effects on cardiac autonomic function in these patients [11]. Furthermore, we have recently presented data demonstrating that patients with reduced left ventricular function (LVF) presented with a more beneficial acute cardiac autonomic adaptation (5 d) at rest compared with patients with normal LVF after inpatient cardiac rehabilitation [12]. Because exercise promotes significant and beneficial cardiac autonomic responses [2,13], investigating acute changes in HRV during exercise performed early after CABG may allow for further insight into autonomic neural regulation and adaptation. In addition, it may help to ensure the most suitable inpatient exercise prescription for patients with different clinical features undergoing this surgical procedure. Therefore, the aim of this study was to investigate whether the same exercise-based inpatient program administered to patients with normal and reduced LVF evokes a similar cardiac autonomic response after CABG. We hypothesize that HRV behavior during the same exercise program differs according to LVF.
Methods Subjects A prospective clinical study was performed within the critical care unit and cardiovascular ward of Irmandade Santa Casa Misericordia Hospital. Human subjects investigation committee approved the study protocol (197/2005) and all patients signed informed consent. The study was registered in Trial RBR-5d877q. The study group consisted of patients with coronary artery disease who had undergone elective CABG carried out with cardiopulmonary bypass. Surgical procedures were performed with the same surgical technique and surgical team. Exclusion criteria included having undergone CABG without cardiopulmonary bypass or concomitant surgery, use of intraaortic balloon pump, previous CABG, myocardial infarction 56 months before CABG, severely depressed LVF [left ventricular ejection fraction (LVEF) 530%], acute significant arrhythmias, coexisting chronic obstructive pulmonary disease, autonomic neuropathy, severe non-cardiac disease, inability or refusal to perform the proposed protocol and any other serious post-operative complaints or illnesses. Patients were classed into two groups according to LVEF values calculated from echocardiography (Teichholz method), performed preoperatively by a highly qualified professional: (1) LVF normal group (LVFN, n ¼ 23), composed of patients with LVEF 55% or (2) LVF-reduced group (LVFR, n ¼ 21), composed of patients with LVEF between 35 and 54%, regarded as mild-to-moderate left ventricular dysfunction secondary to ischemic etiology [14]. Study protocol Clinical variables such as age, sex, weight, height, body mass index, comorbid factors and other relevant clinical features were recorded preoperatively. We also performed a pulmonary function test (spirometry) [15] to investigate the presence of chronic obstructive pulmonary disease [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC)50.7] [16] and applied the validated Baecke questionnaire [17] for the measurement of a person’s habitual physical activity. Information was provided to patients about the effects of surgery on cardiopulmonary function and routine post-operative care, in particular about the inpatient cardiac rehabilitation program. Patients were followed until hospital discharge and the surgical data as cardiopulmonary bypass and aortic
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cross-clamping time, time of surgery and number of grafts were also recorded. Heart rate and the interval between two consecutive heartbeats, defined as the R-R interval (R-Ri), were collected in the afternoon, preoperatively and postoperatively, at rest and during exercise for the analysis of HRV. Procedures Heart rate and R-R interval data acquisition. Heart rate and R-R interval data were recorded by means of a heart rate monitor Polar S810i (Polar Electro TM, Kempele, Finland) at rest and during exercise. Subjects were asked not to participate in physical exercise or ingest caffeinated products prior to and during the experiment. Initially, subjects rested in a sitting position for 10 min. Measurements were subsequently obtained as follows: (1) Rest: Resting measurements were performed in the sitting position preoperatively to characterize baseline autonomic function and repeated the first day after surgery (postoperative day 1, PO1) and the day before discharge. (2) Exercise: Exercise measurements were conducted on PO1, during the extremity range of motion exercises: active flexion– extension exercises of the upper (wrists) and lower (ankles) extremities; five sets of 10 repetitions for each (i.e. totaling 50 repetitions of each) and on the day before hospital discharge during ambulation along a corridor. These exercises were part of the standard inpatient cardiac rehabilitation program applied post-CABG, as described before [11,12]. Before starting each session, subjects were examined and questioned about adverse events (fever, pain, dyspnea, syncope and malaise) that would contraindicate the patient’s participation. A daily assessment (temperature, blood pressure and heart rate) was also performed to ensure that baseline vital signs were within normal limits. In addition, during exercises, the physiotherapists were attentive to the appearance of cyanosis, pallor, tachycardia and bradycardia, and the patients were instructed to promptly report the eventual development of symptoms (excessive fatigue, chest pain and dyspnea) that would lead to cessation of exercise. Signal processing and HRV analysis. After acquisition, the signals were transferred to the Polar Precision Performance Software (Polar Electro OY, Kempele, Finland) and visually inspected and corrected for ectopic beats (premature, supraventricular and ventricular). Periods with more than 10% correction were excluded. Time-series data were processed by Kubios HRV Analysis software version 2 beta (MATLAB, Kuopio, Finland), according to the guidelines put forth by the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology [18]. For analysis, a data set containing 300 sequential R-Ri was selected, discarding the initial 30 s of the exercise signal. The non-linear properties of HRV, capturing the complexity (irregularity) of the dynamic process of heart rate, were analyzed by indices such as (1) correlation dimension, which is the smallest value indicative of the rhythmic data series and therefore, low HRV [19,20]; (2) Shannon entropy [21] and sample entropy [22], which are the highest entropy representing a more unpredictable data series [20,21] and (3) Poincare indices: SD1, which is a measure of short-term HRV, related to parasympathetic modulation and SD2 interpreted as a measure of both short- and longterm HRV (overall HRV) [23]. Linear measures were evaluated by calculating the following indices: (1) mean of RR and its standard deviation (STDRR), (2) integral of the RR histogram divided by the height of the histogram (RR tri) index, (3) baseline width of the RR histogram
DOI: 10.3109/09638288.2013.782362
Cardiac autonomic responses during exercise inpatient program
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(TINN) [18], representing a global index of HRV (overall HRV) and (4) square root of the mean-squared differences of successive RR (rMSSD), which reflect alterations in autonomic tone that are predominantly vagally mediated [24]. Inpatient cardiac rehabilitation program. Postoperatively, all patients followed the supervised once-daily physiotherapy program of early mobilization, from PO1 to hospital discharge, as described before [11,12]. The program began with extremity range of movement exercises on PO1 and ambulation along a hospital corridor from the third day post-surgery, beginning at 5 min and progressing to 10 min for the subsequent days of hospitalization. Throughout the days of hospitalization, the exercise intensity ranged between two and four metabolic equivalents (METs) (for instance, lower extremity range of motion, descending stairs and walking briskly match energy expenditure of &2, 3 and 4 METs, respectively) [25,26], and the heart rate during exercises did not exceed 20 bpm above resting heart rate, in accordance with previous recommendations [26]. In addition, the patients performed voluntary deep-breathing exercises from functional residual capacity to total lung capacity (40 deep breaths in 4 sets of 10, each breath included a 5-s hold at end inspiration) followed by coughs or huffs (with wound support) supervised once daily starting on PO1. Patients were instructed to perform these breathing and coughing exercises independently every waking hour. Statistical analysis Statistical analysis was performed using the STATISTICA version 5.5 (StatSoft, Tulsa, OK). Normality in the distribution of data
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was checked by the Shapiro–Wilks test. Student’s t-test for unpaired and paired comparisons was used for continuous data and Fisher’s exact test was used for categorical data. Statistical significance was denoted by a p-value 50.05. The study sample size was determined using an a value of 0.05 and a power of 80% to detect a difference between LVFN and LVFR groups during exercise for SD2 7 ms and a variability of 8 ms. The estimated sample size was determined to be 20 subjects per group (StatCalc Statistica Soft 5.4.3 2004, AcaStat Software, Leesburg, VA).
Results Importantly, no patients presented with signs and/or symptoms of intolerance to exercise, and no clinical complications were observed during the study. Baseline characteristics A total of 108 patients with a clinical diagnosis of coronary artery disease were being considered for CABG and thus evaluated for possible enrollment in this study. Twenty-three patients were excluded because of not meeting the inclusion criteria and two refused to participate. Hence, 83 patients were included, and from this cohort, 39 were excluded for the reasons described in the flowchart (Figure 1). Finally, 23 patients were assigned to LVFN and 21 to LVFR group for analyses. The baseline characteristics of the study patients are presented in Table 1. With the exception of LVEF, no differences were observed between groups with respect to baseline demographic data, cardiovascular risk profile (i.e. smoking, arterial
Figure 1. Flowchart showing patient’s participation. COPD, chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; LVFN, left ventricular function normal group; LVFR, left ventricular function reduced group; HR, heart rate; HRV, heart rate variability.
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Table 1. Demographic, clinical and surgical data.
Age (years) Male gender, number (%) Weight (kg) Height (m) Body mass index (kg m2) Left ventricular ejection fraction (%) Habitual physical activity, total scorea FEV1/FVC FEV1 (%) Risk factors Smoking history, number (%) Arterial hypertension, number (%) Diabetes mellitus, number (%) Dyslipidemia, number (%) Pharmacological treatment b-blockers, number (%) ACE inhibitors, number (%) Calcium antagonists, number (%) Pre- and post-operative data Cardiopulmonary bypass time (min) Aortic cross clamping time (min) Time of surgery (min) Coronary artery grafts, number Inpatient rehabilitation time (d)
LVFN group (n ¼ 23)
LVFR group (n ¼ 21)
p value
60 9.5 17 (73.9) 75 13 1.6 0.08 27 4.0 61.7 5.7 4.25 1.1 0.85 0.07 93.2 15.0
56 7.8 16 (76.2) 73 14 1.6 0.06 27 5.0 43.8 4.7 4.15 1.2 0.83 0.08 88.4 20.0
0.22 1.00 0.59 0.91 0.66 0.0001 0.80 0.64 0.57
17 18 7 11
(73.9) (78.3) (30.4) (47.8)
15 (65.2) 10 (43.5) 1 (4.3) 68 21 37 14 182 60 2.6 0.6 5.1 1.1
19 15 11 12
(90.5) (71.4) (52.4) (57.1)
0.45 0.73 0.22 0.56
15 (71.4) 8 (38.1) –
0.75 0.76 1.00
69 22 36 12 215 69 2.5 0.6 4.6 0.9
0.70 0.79 0.11 0.82 0.23
Data are presented as mean SD or number (percentage) of subjects. FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; ACE, angiotensin converting enzyme inhibitor; LVFN, left ventricular function normal; LVFR, left ventricular function reduced. a Assessed by the Baecke questionnaire.
Table 2. Baseline (preoperative) heart rate variability data.
Linear HRV Mean RR (ms) STDRR (ms) Mean HR (bpm) rMSSD (ms) RR tri TINN (ms) Non-linear HRV SD1 (ms) SD2 (ms) Shannon entropy Sample entropy Correlation dimension
LVFN group (n ¼ 23)
LVFR group (n ¼ 21)
p value
963 134 20 5.5 63.9 8.6 20 8.2 5.7 1.8 92 29
911 157 15 7.5 68.7 11.0 15 8.2 4.4 1.9 68 34
0.26 0.01 0.13 0.04 0.03 0.02
15 5.6 37 19 3.11 0.4 1.65 0.3 0.81 1.0
9.9 5.2 29 15 3.16 0.3 1.54 0.3 0.40 0.46
0.008 0.17 0.65 0.24 0.06
Data are presented as mean SD; HR, heart rate; HRV, heart rate variability; LVFN, left ventricular function normal; LVFR, left ventricular function reduced; RR, RR intervals; rMSSD, square root of the meansquared differences of successive RR; RR tri, integral of the RR histogram divided by the height of the histogram; STDRR, standard deviation of all RR; TINN, baseline width of the RR histogram.
hypertension, diabetes mellitus and dyslipidemia history), habitual level of physical activity, pharmacological treatment, surgical and hospitalization data, and the number of days of participation in inpatient cardiac rehabilitation. Heart rate variability The characterization of baseline cardiac autonomic function, both by linear and non-linear indices of HRV obtained preoperatively at rest, is listed in Table 2. We observed greater values for some of the HRV measures in the LVFN group compared with the LVFR group (p50.05). An overview of HRV measures assessed on PO1 at rest and during extremity range of movement exercises is listed in Table 3.
Significant intra-group differences were observed for indices of HRV as mean RR (p ¼ 0.0001 and p ¼ 0.02) and mean heart rate (p ¼ 0.0002 and p ¼ 0.03) between rest and exercise to LVFN and LVFR, respectively. No inter-group differences were observed in HRV at rest and during exercise performance. Regarding within-group comparisons between rest and ambulation, we found that some indices decreased significantly during ambulation for both groups: mean RR (754.1 75.1 versus 697.8 83.2 ms), SD1 (7.3 4.0 versus 5.3 2.5 ms) and sample entropy (3.3 0.4 versus 3.9 0.4 ms) in the LVFN group and mean RR (739.8 110.5 versus 678.1 109.1 ms), SD1 (9.5 6.3 versus 5.3 2.3 ms), rMSSD (12.9 8.8 versus 7.4 3.2 ms), RR tri (3.5 1.7 versus 2.1 0.6) and TINN (50.8 25.9 versus 30.6 14.8 ms) in the LVFR group. In addition, the mean HR increased significantly during ambulation compared with rest in both groups: mean HR – 78.3 7.5 versus 87.2 10.6 bpm and 82.7 11.2 versus 90.7 14.4 bpm to LVFN and LVFR, respectively (p 0.01 for all analysis). Table 4 shows the responses of HRV elicited during ambulation on the last hospitalization day in patients with LVFN and LVFR. Lower values were observed for linear (STDRR and TINN, p50.05) and non-linear (SD2, Shannon entropy and correlation dimension, p50.05) indices in the LVFR group compared with the LVFN group. In addition, the results obtained for change in HRV during the transition from rest to ambulation (ambulation to rest) on the day before discharge is illustrated in Figure 2. There were significant differences between groups for all variables shown. The results of medication dosage/day (mg) prescribed postoperatively in the LVFN and LVFR groups were: b-blockers (62.5 24.6 versus 56.6 24.8; p ¼ 0.40); angiotensin converting enzyme inhibitor (ACE) inhibitors (86.2 44.5 versus 62.1 22.0; p ¼ 0.27); calcium antagonists (100 75.5 versus 100 75.5; p ¼ 0.82) and benzodiazepine (12.5 11.0 versus 8 2.6). Furosemide, acetylsalicylic acid and statin were prescribed with the same dosage/day for all patients and
Cardiac autonomic responses during exercise inpatient program
DOI: 10.3109/09638288.2013.782362
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Table 3. Indices of heart rate variability assessed on the first day after surgery at rest and during extremity range of movement exercises in both groups.
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LVFN group (n ¼ 23)
Linear HRV Mean RR (ms) STDRR (ms) Mean HR (1/min) rMSSD (ms) RR tri TINN (ms) Non-linear HRV SD1 (ms) SD2 (ms) Shannon entropy Sample entropy Correlation dimension
LVFR group (n ¼ 21)
Rest
Extremity ROM exercises
Rest
Extremity ROM exercises
716.3 87.5 9.7 6.1 83.4 11.8 8.3 5.1 2.9 1.3 46.1 22.8
679.8 74.9a 9.1 5.5 89.3 9.9a 8.9 5.3 2.7 1.0 50.2 34.1
689.1 103.4 9.4 4.9 87.1 15.2 9.4 6.7 2.8 1.1 43.1 21.0
668.4 105.9a 7.3 4.5 93.0 13.5a 8.4 6.4 2.6 1.3 38.7 22.2
5.9 3.6 20.6 14.0 3.3 0.4 1.3 0.4 0.16 0.3
6.4 3.8 20.4 18.5 3.3 0.4 1.4 0.3 0.14 0.4
7.4 5.6 15.9 6.2 3.2 0.4 1.4 0.3 0.06 0.1
7.0 6.2 15.4 6.1 3.4 0.4 1.5 0.3 0.05 0.1
Data are presented as mean SD; HR, heart rate; HRV, heart rate variability; LVFN, left ventricular function normal; LVFR, left ventricular function reduced; rMSSD, square root of the mean-squared differences of successive RR; ROM, range of movement; RR, RR intervals; RR tri: integral of the RR histogram divided by the height of the histogram; STDRR, standard deviation of all RR; TINN: baseline width of the RR histogram. a Intra-group difference (p50.05). Table 4. Linear and non-linear indices of heart rate variability assessed during ambulation on the last hospitalization day in patients with normal and reduced left ventricular function.
Linear HRV Mean RR (ms) STDRR (ms) Mean HR (1/min) rMSSD (ms) RR tri TINN (ms) Non-linear HRV SD1 (ms) SD2 (ms) Shannon entropy Correlation dimension
LVFN group (n ¼ 23)
LVFR group (n ¼ 21)
p value
697.8 83.2 8.9 4.7 87.2 10.6 8.2 4.1 2.4 0.9 45.8 24.9
678.1 109.1 6.1 2.7 90.7 14.4 7.4 3.2 2.1 0.6 30.6 14.8
0.52 0.04 0.39 0.49 0.23 0.03
5.3 2.5 21.3 9.0 3.9 0.4 0.2 0.2
5.3 2.3 14.8 8.0 3.6 0.5 0.08 0.2
0.94 0.04 0.02 0.02
Data are presented as mean SD; HR, heart rate; HRV, heart rate variability; LVFN, left ventricular function normal; LVFR, left ventricular function reduced; RR, RR intervals; rMSSD, square root of the mean-squared differences of successive RR; RR tri, integral of the RR histogram divided by the height of the histogram; STDRR, standard deviation of all RR; TINN, baseline width of the RR histogram.
were 40, 200 and 40 mg, respectively. Nebulized solution of ipratropium bromide/fenoterol was prescribed similarly between groups (5/15 drops twice daily, morning and evening). The number of individuals receiving medications in the LVFN and LVFR groups were: b-blockers (18 versus 19; p ¼ 0.42); ACE inhibitors (8 versus 7; p ¼ 1.00); calcium antagonists (3 versus 3; p ¼ 1.00); benzodiazepine (10 versus 8; p ¼ 0.77); furosemide (10 versus 6; p ¼ 0.36); acetylsalicylic acid (23 versus 20; p ¼ 0.48); to statin (22 versus 19; p ¼ 0.59) and nebulized solution of ipratropium bromide/fenoterol (5 versus 8; p ¼ 0.32). No statistical difference was observed between groups.
Discussion This study aimed to further investigate the cardiac autonomic response during exercise in patients undergoing CABG according to LVF. To our knowledge, this is the first study to reveal that
the autonomic response elicited by exercise was more attenuated in patients with LVFN. This finding can be verified by lower linear (STDRR and TINN) and non-linear (SD2, Shannon entropy, correlation dimension) indices of HRV in the LVFR group during ambulation. The clinical implications of our results are that the exercise protocol needed to illicit a desirable autonomic response may differ in the CABG population according to LVF. Additionally, the transition analysis (rest to ambulation) further demonstrated smaller values of HRV in the LVFR group suggesting that the commonly utilized exercises for inpatient rehabilitation may be insufficient to elicit a similar autonomic response in CABG patients with LVFN. Exercise is a key component of inpatient cardiac rehabilitation [27]; however, several clinical studies have revealed an attenuation of indices of HRV after CABG [3–7], with consequent electrical instability and increased risk of adverse events [6,9,10]. Thus, investigating HRV during exercise would allow for a better understanding of autonomic responses, potentially allowing for the ability to provide a more appropriate and individualized exercise program during the acute phase of surgical recovery in this patient population. Previous studies have demonstrated that physical exercises during inpatient rehabilitation could ameliorate cardiac autonomic imbalance after acute myocardial infarction [28], as well as post-CABG [11]. However, autonomic adaptations were previously evaluated at rest and after completion of the exercise protocols. Thus, to our knowledge, this is the first study to describe the cardiac autonomic response during physical exercise performed during the inpatient phase of cardiac rehabilitation in patients after CABG. Additionally, our previous study [12] showed that resting LVF influences the autonomic adaptations after a rehabilitation protocol (5 d). However, the autonomic response in patients with different LVF during exercise had yet to be investigated. In this sense, this study demonstrates a more attenuated autonomic response to exercise in patients with LVFN. During exercise, alterations in cardiac autonomic function must occur to match cardiac output to tissue perfusion [2]. In this context, the magnitude of adjustments appears to be dependent on the characteristics of the exercise stimulus [2,29]. Previous studies demonstrated that these responses depend on the intensity of physical activity, where the modulation of parasympathetic
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Figure 2. Heart rate variability indices change (ambulation to rest) on day before discharge of patients with normal and reduced left ventricular function. (A) STDRR, (B) SD2, (C) rMSSD, (D) RR tri, (E) TINN, and (F) correlation dimension.
activity progressively declines, until there is complete withdrawal at approximately 50–60% of peak aerobic capacity, at which time sympathetic activity begins to increase [30–32]. In this study, for the same type of exercise (ambulation), an attenuated response was observed in the LVFN group, because the LVFR group showed a marked reduction in the index representing parasympathetic activity (rMSSD) and indices related to total HRV (SD2, RR tri, TINN and STDRR). A decrease in HRV indices during physical exercise is an expected behavior to provide necessary increases in heart rate, stroke volume, blood pressure and cardiac output [33]. In this context, our results demonstrate less need for cardiovascular adjustments in post-CABG patients with LVFN compared with those with LVFR. The non-linear indices related to cardiovascular complexity also demonstrated lower values in subjects with LVFR during ambulation, and in accordance with our findings, it has been suggested that vagal withdrawal is a more important modulator of non-linear deterministic regulation [34]. However, other authors have shown reduced HRV complexity in sympathetic activation conditions (i.e. head-up tilt, dynamic cycling exercise and isometric handgrip exercise), making it difficult to understand the exact contributions of the autonomic
nervous system branches to non-linear fluctuations in heart rate, because the conditions associated with sympathoexcitation may also be linked to vagal withdrawal [35,36]. However, in our study, we only observed a reduction in the indices related to suppression of parasympathetic modulation, which we attribute to the low exercise intensity employed in the current study protocol. The inter-group differences observed in the autonomic response induced by exercise may be related to the fact that, during ambulation, repositioning from sitting to standing, by itself, reduces central venous pressure with a consequent reduction in stroke volume (Frank Starling mechanism). Moreover, at the onset of ambulation, although muscle contraction (calf muscles) acts to restore venous return, normalizing central venous pressure and cardiac output, oxygen consumption rises requiring a readjustment of the cardiac output [37]. So, we can say that for the exercise protocol used in this study, autonomic adjustments were more pronounced for patients with impaired LVF. The increase in oxygen demand induced by early mobilization after cardiac surgery can be compensated by the combination of increased cardiac index and oxygen extraction, according to Kirkeby-Garstad et al. [38]. However, these authors did not evaluate the cardiac autonomic response, which would
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DOI: 10.3109/09638288.2013.782362
Cardiac autonomic responses during exercise inpatient program
have allowed for a comparison with our findings. In this study, measurements of cardiac output and mixed venous oxygen saturation would allow for a more precise description of compensatory responses. Other studies evaluated the response of constant load lowintensity exercise in post-CABG patients during outpatient cardiac rehabilitation, also finding a reduction in parasympathetic modulation without evidence of increased sympathetic modulation [31]. In our study, we observed an attenuated reduction in vagal activity in the LVFN group compared with the LVFR group, although both groups performed the same rehabilitation protocol, which involved an energy expenditure of approximately four METs (14 ml O2 kg1 min1). However, energy expenditure was not directly assessed to verify possible differences that could influence our findings. Based on our findings, the exercise protocol applied in the current study to post-CABG patients with LVFN seems to be insufficient to evoke autonomic responses when compared with patients with LVFR. Additionally, our previous study [12] demonstrated that patients with LVFR showed better cardiac autonomic adaptation, assessed at rest after rehabilitation program which included physical exercise (5 d), suggesting that the exercises applied may have limited benefits for the LVFN group. In this context, we speculate that a higher exercise volume than that used in this study in post-CABG patients with LVFN may be more appropriate, a hypothesis that warrants further investigation. It is important to note that during extremity range of motion exercises (approximately two METs), although there was an increase in heart rate and conversely a reduction in mean RR in both groups, no other HRV changes were found, different from that observed during the ambulation analysis. This indicates that the modulatory effect on control of HR is differently affected by dynamic exercise of different intensity and size of active muscle mass [29]. CABG is a traumatic event that has been associated with mental stress, anxiety and depression [39]. Previous research indicates that this surgical procedure may direct influence autonomic nervous system regulation [40]. Given that subjective perception of adverse symptoms is a common post-CABG and can influence HRV, assessment of patients’ perceptual status by structured interviews or self-administered questionnaires would be interesting. However, this was not evaluated in the current study and should be considered a potential confounding factor. Several studies have suggested that drugs such as b-blockers, ACE inhibitors and calcium channel blockers may modulate autonomic nervous system activity [41–43]. Considering this pharmacology impact on cardiac autonomic modulation, we performed a statistical analysis on dosage and number of individuals who were receiving the prescribed medications postoperatively (pre-discharge) in both groups. We verified that the postoperative medication regimen was similar in both groups. Thus, the results of the current study do not appear to be attributed to drug effects on autonomic modulation of heart rate.
Limitations This study has methodological limitations which must be acknowledged. First, patients with severely reduced LVF (LVEF530%) were not included. Second, the respiratory variables (respiratory rate and tidal volume) were not controlled and additional parameters to evaluate the exercise intensity employed were not used (e.g. Borg’s scale, rate pressure product). The addition of a control group might have added useful information to the study, although its absence does not invalidate the present findings.
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In summary, we conclude that physical exercise during inpatient cardiac rehabilitation, performed by post-CABG patients who have LVFN, triggered a more attenuated cardiac autonomic response when compared with patients with LVFR. Thus, the exercise prescription during the acute phase of rehabilitation may benefit from titration according to LVF. We hypothesize that increasing the exercise volume of the proposed protocol (number of sets, repetitions, duration of exercise and/or rate of progress) for patients with LVFN would result in better autonomic outcome. However, it was not possible to establish an optimal exercise prescription for these patients, because this study was not designed to investigate different protocol, which is an avenue for future studies.
Acknowledgements The authors are grateful to the UFSCar Cardiopulmonary Laboratory and Santa Casa of Araraquara Hospital staff for their enthusiastic help. The authors also extend their special thanks to the subjects for their participation. This study was supported by the Sao Paulo Foundation for Research Support (FAPESP, process 05/59427-7 and 09/54194-5) and by the Brazilian National Council for Scientific and Technological Development (CNPq).
Declaration of interest The authors report no declarations of interest.
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