Impact of Early Ambulation on the Prognosis of Coronary Artery Bypass Grafting Patients

Abstract

Background: The effect of delayed ambulation on the outcome of coronary artery bypass grafting (CABG) remains to be clarified.

Methods and Results: The long-term and in-hospital outcomes of 887 patients who underwent isolated CABG (455 off-pump cases, 135 urgent cases) were evaluated, with a focus on the timing of first ambulation. In-hospital mortality cases were excluded. Early ambulation (first ambulation within 3 days after operation) was achieved in 339 (38%) patients. In the multivariable logistic regression analysis, longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. Delayed ambulation was associated with a high incidence of postoperative complications, such as pneumonia, and stroke (P<0.01). Following discharge, 22.2% of patients experienced major cardiac events and 13.8% died during the follow-up period (median follow-up 60 months). Cox hazards analysis revealed that delayed ambulation was associated with long-term adverse events (hazard ratio 1.04 per day, P<0.001). With adjustment for preoperative factors, the estimated future risk of adverse events was found to be increased day-by-day during the delay until initial ambulation.

Conclusions: In isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation protocol after cardiac surgery.

More than 70,000 patients undergo cardiac surgery annually in Japan,¹ and postoperative rehabilitation after coronary artery bypass grafting (CABG) can improve exercise tolerance, coronary risk factors, autonomic activity, cardiac function, and bypass patency.^1,2 It has also been revealed that exercise therapy after cardiac surgery should be initiated as early as possible for recovery of the patient’s functional status, but postoperative complaints, such as pain, dizziness, nausea, vomiting, and fainting, often cause delayed ambulation after surgery.^3,4 It has also been reported that age,⁵ level of physical activity,⁶ preoperative exercise tolerance,⁷ intraoperative blood loss,⁸ postoperative complications,⁹ and operative time are associated with delayed ambulation. Although there are some reports analyzing the factors associated with delayed ambulation, few have investigated the effect of postoperative early ambulation on outcomes.

We analyzed the factors associated with delayed ambulation in patients who underwent isolated CABG and to investigated the effect of postoperative early ambulation on late clinical outcomes.

Methods

Inclusion and Exclusion Criteria for Patients

Patients who underwent isolated CABG at Nagoya University Hospital between 2002 and 2018 were included in this study. In-hospital mortality cases (n=31) were excluded. After applying this exclusion criterion, 887 patients who underwent isolated CABG were evaluated retrospectively for their long-term and in-hospital outcomes based on medical records. This study was approved by the Institutional Review Board (IRB No. 2020-0060), which waived the requirement of individual consent. Here we report on experiments on human subjects in accordance with the ethical standards of the “Declaration of Helsinki” and the Committee in charge of human experimentation.

Definition of Outcomes, and Evaluation of Ambulation

Unless otherwise stated, the definitions of preoperative risks and postoperative outcomes were based on the Japan Adult Cardiovascular Surgery Database protocols.¹⁰ Composite preoperative risk was evaluated by EuroSCORE II. After the operation, ambulation was attempted with the guidance of professional physiotherapists based on current guidelines.^11,12 Specifically, based on the standard progression of rehabilitation after cardiac surgery in the Guidelines for Rehabilitation in Cardiovascular Diseases (the joint guidelines of the Japanese Society of Cardiology and the Japanese Society of Cardiac Rehabilitation), we proceeded with the following on the first postoperative day: self-movement of limbs, passive sitting, breathing practice, as well as 10-minute sitting on the first and second postoperative days. Patients practiced sitting on the edge of the bed for 10 min and then standing foot stomping for 1–2 sets on the first and second postoperative days, with ambulation on the second and third postoperative days. The criteria for starting bed withdrawal were also based on the guidelines for bed withdrawal after cardiac surgery: surgery: (1) low output syndrome (LOS); (2) insertion of a Swan-Ganz catheter; (3) resting heart rate ≥120 beats/min; (4) unstable blood pressure (blood pressure falls only by changing positions); (5) unstable hemodynamics; and (6) unstable pulse. Weaning the patient from the bed was initiated if the above-mentioned criteria were satisfied, in the absence of the following conditions: (1) unstable hemodynamic arrhythmia; (2) dyspnea or tachypnea at rest (respiratory rate <30 breaths/min); and (3) continued postoperative bleeding tendency. Based on the guidelines, “early ambulation” was defined as first ambulation within 3 days after surgery (Group E) and delayed ambulation was defined as ambulation after 4 days (Group D).^11,12

After discharge, patients were followed in the outpatient clinic of Nagoya University Hospital or at an affiliated hospital/clinic on regular basis. For long-term outcomes, the primary endpoint was “cardiac event-free survival”. Cardiac events were defined as: heart failure, myocardial ischemic event (including myocardial infarction), or arrhythmic event requiring hospitalization.

Statistical Analysis

Continuous variables are expressed as the mean and standard deviation, and categorical variables are expressed as the number and percentage. Continuous variables were analyzed using the Mann-Whitney U-test, and categorical variables by Fisher’s exact test. Multivariable logistic regression analysis was performed to assess the factors associated with delayed initial ambulation. Kaplan-Meier curves were plotted, and the log-rank test was performed to compare the outcome for all-cause death and cardiac events in the 2 groups. In addition, we performed univariate and multivariable Cox regression analyses to estimate the hazard ratio (HR) of first ambulation for all-cause death and cardiac events. In the Cox regression analysis, EuroSCORE II, body mass index, and operation time were selected as known prognostic factors with reference to previous studies that described clinically necessary variables.^13,14 Moreover, to visualize the estimated effect of each first ambulation day, we conducted a Cox regression analysis with spline functions for all-cause death, with adjustment for risk factors for cardiac events. Statistical analyses were performed using R version 3.55 (R Foundation for Statistical Computing, Vienna, Austria). In all analyses, two-tailed P values <0.05 were considered to indicate statistical significance.

Results

The baseline patient characteristics and in-hospital outcomes are summarized in Table 1. In the overall study population, the mean age was 68.6±9.1 years and the mean EuroSCORE II was 3.6±6.4. Early ambulation (first ambulation within 3 days of operation) was achieved in 339 (38.2%) patients (Group E). This cohort included 135 urgent non-elective surgery cases and 455 (51.3%) off-pump cases.

Table 1. Preoperative Baseline Patient Characteristics

	Overall (n=887)	Group E (n=339)	Group D (n=548)	P value
Age, years	68.6±9.1	67.9±9.4	70.0±8.9	0.086
Male, %	689 (77.7)	269 (79.4)	420 (76.6)	0.362
BMI, kg/m2	23.7±3.5	23.7±3.4	23.8±3.6	0.884
<18.5, %	44 (5.0)	15 (4.4)	29 (5.3)	0.635
Renal dysfunction, %	194 (21.9)	44 (13.0)	150 (27.4)	<0.001
COPD, %	41 (4.6)	17 (5.0)	24 (4.4)	0.742
Peripheral artery disease, %	237 (26.7)	74 (21.8)	163 (29.7)	0.010
Neurological dysfunction, %	80 (9.0)	30 (8.8)	50 (9.1)	1.000
Recent myocardial infarction, %	121 (13.6)	20 (5.9)	101 (18.4)	<0.001
Preoperative shock aid resuscitation, %	98 (11.0)	9 (2.7)	89 (16.2)	<0.001
LVEF, %	58.3±13.5	60.7±11.6	56.8±14.3	<0.001
6MWD, m (n=411)	351.8±113.0	368.9±107.5	333.7±116.1	0.002
≥300 m, %	285 (69.3)	161 (76.3)	124 (62.0)	0.002
Elective, %	752 (84.8)	318 (93.8)	434 (79.2)	<0.001
EuroSCORE II	3.6±6.4	2.0±2.7	4.7±7.7	<0.001

Group E, first ambulation within 3 days; Group D, first ambulation ≥4 days. BMI, body mass index; COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction; 6MWD, 6-minute walk distance.

In comparison with Group E, the delayed ambulation patients (≥4 days) (Group D) showed a shorter 6-minute walk distance (6MWD: Group E 368.9 m vs. Group D 333.7 m, P=0.002), poor ejection fraction before operation (Group E vs. Group D: 60.7 vs. 56.8; P<0.001). Operation time was longer in Group D (Group E 5.6 h vs. Group D 6.1 h, P<0.001) but the percentage of off-pump CABG was similar between groups (Group E 49.0% vs. Group D 52.7%, P=0.3).

Not surprisingly, Group D showed a significantly higher incidence rate of postoperative complications, such as re-thoracotomy, pneumonia, and longer intubation (P<0.05). Baseline variables with P values <0.1 in the univariate analysis were included in the multivariable analysis. The multivariable logistic regression analysis identified longer operation time, urgent case, EuroSCORE II, re-thoracotomy, and respiratory time as factors associated with delayed initial ambulation (Table 2).

Table 2. Adjusted Logistic Regression Analysis for First Ambulation ≥4 Days

	Multivariable analysis
	Odds ratio	95% CI	P value
Elective	0.53	0.30–0.93	0.027
EuroSCORE II	1.13	1.05–1.22	<0.001
Operation time, h	1.16	1.05–1.28	<0.001
Re-thoracotomy	0.56	0.34–0.91	0.020
Complications of AF	1.10	0.61–1.99	0.760
Pneumonia	0.22	0.03–1.93	0.171
Complications of stroke	4.52	0.53–38.30	0.167
Respiratory time, h	10.80	1.43–81.70	0.021

AF, atrial fibrillation; CI, confidence interval.

Following discharge, 22.2% of patients experienced major cardiac events (heart failure n=133, myocardial ischemic event n=56, arrhythmic event requiring intervention, n=8) and 13.8% of patients died during follow-up (median follow-up 60 months). Of the 122 deaths, the causes were cardiac death (n=32), cancer (n=29), pneumonia (n=19), stroke (n=12), other (n=12), and unknown (n=18). The incidence of such long-term events was significantly higher in Group D (Group E vs. Group D: 9.4% vs. 16.4%; P=0.004) (Table 3). Figure 1 showed the cumulative cardiac event-free survival rate. Group D exhibited worse long-term outcomes (P=0.044, log-rank).

Table 3. Postoperative Baseline Patient Characteristics

	Overall (n=887)	Group E (n=339)	Group D (n=548)	P value
No. of lesion branches	2.7±0.5	2.6±0.6	2.7±0.5	0.006
No. of coincident branches	2.8±1.0	2.8±1.0	2.8±1.0	0.275
Operation time, h	5.9±1.7	5.6±1.6	6.1±1.8	<0.001
Off-pump CABG, %	455 (51.3)	166 (49.0)	289 (52.7)	0.300
Cross-clamp time, min (n=432)	107.3±41.6	107.1±37.6	107.5±44.2	0.929
Cardiopulmonary bypass time, min (n=491)	159.4±47.6	152.2±39.2	164.4±51.5	0.003
Re-thoracotomy, %	315 (35.5)	75 (22.1)	240 (43.8)	<0.001
Complications of disabling stroke, %	13 (1.5)	1 (0.3)	12 (2.2)	0.022
Complications of stroke, %	18 (2.0)	1 (0.3)	17 (3.1)	0.003
Complications of renal failure, %	22 (2.5)	4 (1.2)	18 (3.3)	0.073
Complications of AF, %	158 (17.8)	44 (13.0)	114 (20.8)	0.003
Mediastinitis, %	16 (1.8)	3 (0.9)	13 (2.4)	0.125
Pneumonia, %	18 (2.0)	1 (0.3)	17 (3.1)	0.003
Prolonged ventilation >24 h	60 (6.8)	1 (0.1)	59 (10.7)	<0.001
ICU stay, days	2.8±4.2	1.3±0.6	3.7±5.2	<0.001
Respiratory time, h	27.6±86.0	8.8±4.7	39.6±108.3	<0.001
Hospital stay, days	23.4±17.7	17.9±8.4	26.8±20.8	<0.001
All-cause death, %	122 (13.8)	32 (9.4)	90 (16.4)	0.004
All-cause death or CAG, PCI, HF, arrhythmia, %	197 (22.2)	54 (15.9)	143 (26.2)	<0.001
Time to first ambulation, days	5.3±5.7	2.7±0.5	7.0±6.7	<0.001

Group E, first ambulation within 3 days; Group D, first ambulation ≥4 days. AF, atrial fibrillation; CABG, coronary artery bypass grafting; CAG, coronary angiography; HF, heart failure; ICU, intensive care unit; PCI, percutaneous coronary intervention.

Figure 1.

Kaplan-Meier curves of cumulative (A) and cardiac event-free (B) survival according to whether the first postoperative ambulation was within 3 days.

Table 4 shows the results of the Cox regression analysis for late death and cardiac events. Delayed postoperative ambulation was significantly associated with late death (adjusted HR per 1-day delay in postoperative ambulation: 1.04; 95% CI: 1.02–1.06; P=0.001), even after adjustment for body mass index <18.5, EuroSCORE II, and operative time (Supplementary Table). With adjustment for preoperative factors, the estimated future risk of adverse events was found to increase day-by-day during the delay until initial ambulation. The association between days to postoperative ambulation and cardiac events, including late death is shown in Figure 2. Cardiac events and late death increased as the first postoperative ambulation was delayed. Regarding the results of the spline analysis, there was a tendency for the number of cases to rise steadily until the 20th, but then level off or fall. Because there were almost no cases after day 20, the spline analysis may have been unable to accurately estimate the HR. In addition, the HR itself did not change significantly, regardless of the time interval between the 3rd, 4th, and 5th days.

Table 4. Unadjusted and Adjusted Cox Regression Analyses for All-Cause Death

Variable	Univariate analysis			Multivariable analysis
	HR	95% CI	P value	HR	95% CI	P value
BMI <18.5	0.41	0.24–0.71	0.001	0.64	0.34–1.19	0.157
EuroSCORE II	1.03	1.01–1.04	<0.001	1.01	0.99–1.03	0.144
Operation time, h	0.79	0.70–0.89	<0.001	0.80	0.71–0.91	<0.001
Time to first ambulation, days	1.04	1.02–1.06	<0.001	1.04	1.02–1.06	<0.001

BMI, body mass index; CI, confidence interval; HR, hazard ratio.

Figure 2.

Results of the Cox spline regression analysis. The estimated spline function in the hazard ratio on the effect of the day of first ambulation for all-cause death (A) and cardiac events (B). The hazard ratio (solid line) and 95% confidence interval (orange dashed lines) were estimated in a Cox multivariable model with the day to first ambulation represented as a spline function. Red dashed lines represent HR=1. CABG, coronary artery bypass grafting; CAG, coronary angiography; PCI, percutaneous coronary intervention; HF, heart failure.

Discussion

The present study showed that delayed ambulation (HR 1.04 per day, P=0.001) was associated with long-term adverse events. By adjusting for preoperative factors, the estimated risk of future adverse events was found to increase day-by-day during the delay until initial ambulation. Similarly, Ishikawa et al¹⁵ and Kono et al¹⁶ conducted studies of patients hospitalized for acute heart failure. When the start of ambulation was delayed, cardiovascular events also increased in addition to prolongation of hospitalization and re-hospitalization. They pointed out that a decrease in skeletal muscle mass during hospitalization may be a cause of the problem.

Abdullahi et al stated that low preoperative frailty and physical activity scores in open heart surgery patients were associated with increased early postoperative complications and prolonged hospital stay.¹⁷ Kamiya et al¹⁸ showed that high quadriceps muscle strength after CABG was associated with cardiac-related death after hospital discharge. They reported that for every 10% increase of body weight in quadriceps muscle strength, the risk of cardiovascular death decreased by 34%. In the field of cardiac surgery, there may also be a relationship between loss of skeletal mass and a worse mid-term prognosis. The patients enrolled in that study were different from the patient population of our study. However, the results were similar to those of our present study with regard to the association of a delay in the start of ambulation and an increase in cardiac events after hospital discharge. It is possible that in the present study, rather than delayed first ambulation itself increasing all-cause mortality after surgery, the patients with delayed first ambulation were actually at potential risk for all-cause death. After surgery, a delay in first ambulation may serve as an indicator of potential frailty. Previous studies have reported that delayed postoperative gait initiation is associated with hospitalization-related disability in patients undergoing cardiac surgery.¹⁹ In the present study, the HR itself did not change significantly, regardless of the time interval between the 3rd, 4th, and 5th days, and the results of the 6MWD showed that patients with normal physical function (SPPB ≥10) started ambulation on or after the 3rd day, while those with low physical function (SPPB ≤9) started ambulation on or after the 6th day. In addition, there have been reports on hospitalization-related disability and prognosis,²⁰ and we believe that hospitalization-related disability may mediate delayed ambulation and poor prognosis, and influence the poor long-term prognosis. Although it is both a cause and a consequence, it is true that delayed first ambulation is often associated with complications.

Study Limitations

The present study has several limitations, including its single-center nature and the fact that only Asian patients who underwent CABG were included in the analysis. Because this study was conducted retrospectively, it was difficult to determine the causal relationship between delayed onset of ambulation and prognosis. In addition, confounding factors that prevent patients from ambulation, such as frailty and physical activity, could not be completely eliminated. In addition, the accuracy of some variables depended on the accuracy of medical records. The results of this study suggest that it is more likely that patients with delayed first ambulation had an increased potential risk of future events rather than delayed first ambulation itself increasing cardiac events. Therefore, the effect of early ambulation for all-cause death and cardiac events needs further evaluation in future studies.

Conclusions

A longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. In addition, in isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation following cardiac surgery.

Conflict of Interest Statement

The authors certify that no affiliation or financial involvement exists between them and any organization with a direct interest in the subject matter or materials discussed in the article.

Disclosures

The authors affirm that they have no financial or personal affiliations (including research funding) or other involvement with any commercial organization that has a direct financial interest in any matter included in this manuscript.

IRB Information

This study was approved by the Ethics Committee of Nagoya University Hospital (IRB No. 2020-0060).

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-22-0416

References

• 1.   Nakai Y, Kataoka Y, Bando M, Hiasa Y, Taki H, Harada M, et al. Effects of physical exercise training on cardiac function and graft patency after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1987; 93: 65–72, doi:10.1016/s0022-5223(19)36476-1.
• 2.   Spiroski D, Andjić M, Stojanović OI, Lazović M, Dikić AD, Ostojić M, et al. Very short/short-term benefit of inpatient/outpatient cardiac rehabilitation programs after coronary artery bypass grafting surgery. Clin Cardiol 2017; 40: 281–286, doi:10.1002/clc.22656.
• 3.   Das-Neves-Pereira JC, Bagan P, Coimbra-Israel AP, Grimaillof-Junior A, Cesar-Lopez G, Milanez-de-Campos JR, et al. Fast-track rehabilitation for lung cancer lobectomy: A five-year experience. Eur J Cardiothorac Surg 2009; 36: 383–392, doi:10.1016/j.ejcts.2009.02.020.
• 4.   Mizota T, Tanaka T, Koyama T, Iwata Y, Fukuda K, Daijo H. Orthostatic intolerance during early mobilization following video-assisted thoracic surgery. J Anesth 2013; 27: 895–900, doi:10.1007/s00540-013-1634-4.
• 5.   Maruyama Y, Inoue K, Mitsuka Y, Hashimoto T, Makuuchi M, Nagashima D, et al. Applicability of enhanced recovery program for advanced liver surgery. World J Surg 2014; 38: 2676–2682, doi:10.1007/s00268-014-2613-0.
• 6.   Hayashi K, Hirashiki A, Kodama A, Murohara T, Shimizu M, Kondo T, et al. Impact of preoperative regular physical activity on postoperative course after open abdominal aortic aneurysm surgery. Heart Vessels 2015; 31: 578–583, doi:10.1007/s00380-015-0644-6.
• 7.   Hayashi K, Fukumoto K, Yokoi K, Nagaya M, Inoue T, Ito S, et al. Post-operative delayed ambulation after thymectomy is associated with pre-operative six-minute walk distance. Disabil Rehabil 2018; 40: 1900–1905, doi:10.1080/09638288.2017.1315182.
• 8.   Oh HK, Ihn MH, Son IT, Park JT, Lee J, Kim DW, et al. Factors associated with failure of enhanced recovery programs after laparoscopic colon cancer surgery: A single-center retrospective study. Surg Endosc 2016; 30: 1086–1093, doi:10.1007/s00464-015-4302-y.
• 9.   Boulind CE, Yeo M, Burkill C, Witt A, James E, Ewings P, et al. Factors predicting deviation from an enhanced recovery programme and delayed discharge after laparoscopic colorectal surgery. Colorectal Dis 2012; 14: 103–110, doi:10.1111/j.1463-1318.2011.02799.x.
• 10.   Tokuda Y, Miyata H, Motomura N, Oshima H, Usui A, Takamoto S. Brain protection during ascending aortic repair for stanford type A acute aortic dissection surgery: Nationwide analysis in Japan. Circ J 2014; 78: 2431–2438, doi:10.1253/circj.CJ-14-0565.
• 11.   Makita S, Yasu T, Akashi YJ, Adachi H, Izawa H, Ishihara S, et al; on behalf of the Japanese Circulation Society/the Japanese Association of Cardiac Rehabilitation Joint Working Group. JCS/JACR 2021 guideline on rehabilitation in patients with cardiovascular disease. Circ J 2023; 87: 155–235, doi:10.1253/circj.CJ-22-0234.
• 12.   JCS Joint Working Group. Guidelines for rehabilitation in patients with cardiovascular disease (JCS 2012). Circ J 2014; 78: 2022–2093, doi:10.1253/circj.CJ-66-0094.
• 13.   Kattih B, Carstens DC, Boeckling F, Rasper T, Pergola G, Dimmeler S, et al. Low circulating musclin is associated with adverse prognosis in patients undergoing transcatheter aortic valve implantation at low-intermediate risk. J Am Heart Assoc 2022; 11: e022792, doi:10.1161/JAHA.121.022792.
• 14.   Endo D, Yamamoto T, Kajimoto K, Matsushita S, Dohi S, Shimada A, et al. Coronary artery bypass grafting in patients with chronic kidney disease: Chronic kidney disease has an independent adverse effect on the long-term outcome of coronary artery bypass grafting. Biomed Res Int 2022; 2022: 4994970, doi:10.1155/2022/4994970.
• 15.   Ishikawa K, Fukushima A, Yokota T, Takada S, Furihata T, Kakutani N, et al. Clinical impact and associated factors of delayed ambulation in patients with acute heart failure. Circ Rep 2019; 1: 179–186, doi:10.1253/circrep.cr-18-0022.
• 16.   Kono Y, Izawa H, Aoyagi Y, Ishikawa A, Sugiura T, Mori E, et al. Predictive impact of early mobilization on rehospitalization for elderly Japanese heart failure patients. Heart Vessels 2020; 35: 531–536, doi:10.1007/s00380-019-01517-8.
• 17.   Abdullahi YS, Salmasi MY, Moscarelli M, Parlanti A, Marotta M, Varone E, et al. The use of frailty scoring to predict early physical activity levels after cardiac surgery. Ann Thorac Surg 2021; 111: 36–43, doi:10.1016/j.athoracsur.2020.06.029.
• 18.   Kamiya K, Masuda T, Tanaka S, Hamazaki N, Matsue Y, Mezzani A, et al. Quadriceps strength as a predictor of mortality in coronary artery disease. Am J Med 2015; 128: 1212–1219, doi:10.1016/j.amjmed.2015.06.035.
• 19.   Hori K, Usuba K, Sakuyama A, Adachi Y, Hirakawa K, Nakayama A, et al. Hospitalization-associated disability after cardiac surgery in elderly patients: Exploring the risk factors using machine learning algorithms. Circ Rep 2021; 3: 423–430, doi:10.1253/circrep.cr-21-0057.
• 20.   Saitoh M, Takahashi Y, Okamura D, Akiho M, Suzuki H, Noguchi N, et al. Prognostic impact of hospital-acquired disability in elderly patients with heart failure. ESC Heart Fail 2021; 8: 1767–1774, doi:10.1002/ehf2.13356.