Eur J Cardiothorac Surg 2009;35:235-240. doi:10.1016/j.ejcts.2008.10.043
Copyright © 2009, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
Cardiopulmonary bypass and left ventricular systolic dysfunction impacts operative mortality differently in elderly and young patients
Dumbor L. Ngaage*,
Michael E. Cowen,
Alexander R. Cale
Castle Hill Hospital, Kingston-Upon-Hull, East Yorkshire, United Kingdom
Received 18 August 2008;
received in revised form 23 October 2008;
accepted 28 October 2008.
* Corresponding author. Address: Department of Cardiothoracic Surgery, Castle Hill Hospital, Kingston-Upon-Hull, East Yorkshire HU16 5JQ, United Kingdom. Tel.: +44 1482 623256; fax: +44 1482 623257. (Email: dngaage{at}yahoo.com).
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Abstract
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Objective: Cardiac surgery is higher risk in the elderly. It has been suggested that preoperative left ventricular systolic dysfunction (LVSD) and cardiopulmonary bypass (CPB) affect elderly and young patients differently. This study investigates the predictive risk of preoperative LVSD and CPB time for operative mortality in the two groups of patients. Methods: We reviewed the data for 2616 consecutive patients aged 
70 years and 4078 young patients who had coronary artery bypass grafting (CABG) and/or valve surgery between March 1998 and January 2007. Subgroups defined by severity of LVSD (ejection fraction >0.50 [mild], 0.31–0.50 [moderate] and 
0.30 [severe]) were analysed. Logistic regression models were constructed to identify risk factors among elderly and young patients. Results: Elderly patients were higher risk and more often underwent valve operation. Moderate and severe LVSD were present in 22% (n
= 566) and 6% (n
= 155) of elderly compared to 18% (n
= 739) and 5% (n
= 215) of young patients (p
= 0.001). Operative mortality for CABG was higher in elderly patients with mild (2.3% vs 0.7%, p
< 0.0001), moderate (4.7% vs 2.3%, p
= 0.04) and severe LVSD (13.5% vs 8.8%, p
= 0.01). Although CPB times for similar procedures were equivalent for the two groups, procedure-specific mortality rates were higher among elderly patients for all operations. Whereas age (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.03–1.15, p
= 0.002) and CPB time (OR 1.01, 95% CI 1.0–1.02, p
< 0.0001) were predictors for operative mortality for the elderly, they (age [OR 1.0, 95% CI 0.96–1.05, p
= 0.87], CPB time [OR 1.0, 95% CI 1.0–1.01, p
= 0.17]) were not for young patients. Moderate LVSD was a risk factor for young patients (OR 3.01, 95% CI 1.45–6.26, p
= 0.003) but not for the elderly (OR 1.33, 95% CI 0.77–2.29, p
= 0.30). Conclusion: Differences in the significance of risk factors between elderly and young patients contribute to the disproportionate operative mortalities. Our data showed that age and CPB duration increased the risk of operative mortality only in the elderly, but the impact of moderate, unlike severe, LVSD was tempered. Further studies are warranted to investigate more biocompatible bypass systems in elderly patients, and if current risk stratification should, perhaps, be revised for elderly patients.
Key Words: Elderly • Operative mortality • Left ventricular systolic dysfunction • Cardiopulmonary bypass
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1. Introduction
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Surgery in the elderly, a growing prospect of cardiac surgery, is challenged by comparatively higher operative morbidity and mortality [1,2]. Advanced age and high prevalence of extra-cardiac comorbidities have been identified as risk factors contributing to these adverse outcomes in the elderly [3]. Age has a profound influence on surgical outcomes and, in patients with advanced age the importance of other risk factors may be affected [4]. For example, it has been suggested that the influence of gender on operative outcome may be diminished in octogenarians [5]. It is uncertain if this is due to the singular effect of the physiological decline associated with aging or the additional influence of prevalent pathophysiologies in the elderly.
Left ventricular systolic dysfunction (LVSD) is a well recognised determinant of operative mortality after cardiac surgery regardless of age, and has a direct bearing on operative decisions and strategies [6,7]. The majority of elderly patients undergoing cardiac surgery present with LVSD [8]. Non-surgical studies [9,10] have reported a decline in the prognostic influence of LVSD with increasing age, but this phenomenon has not been investigated in surgical patients and is relevant in current practice. Furthermore, age-related differences in systemic response to cardiopulmonary bypass (CPB) have been shown to result in suppression of myocardial performance in the elderly [11]. We, therefore, undertook this study to assess; (1) the predictive risk of preoperative LVSD (mild, moderate and severe) and, (2) the influence of CPB duration on operative mortality in elderly (70 years) and young (<70 years) patients.
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2. Methods
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Over 100 clinical data are prospectively collected for all patients undergoing cardiac surgery at our university teaching hospital, and stored in a departmental database managed by dedicated trained staff that regularly validate the entries. After study approval and patient consent waiver were obtained from the medical and ethics committee of our institution, data were retrieved from the database for all patients who underwent primary coronary artery bypass grafting (CABG) and/or valve replacement/repair from March 1998 through January 2007. Details of left ventricular systolic function and CPB were available for 6694 (out of 6971) patients and they constitute the study cohort. Two groups were defined on the basis of age; elderly if 70 years, and young if <70 years. Data relating to demographics, symptoms, cardiac morbidity, comorbidities, operative procedures and postoperative complications including in-hospital death, were compared between the two groups. On the basis of left ventricular ejection fraction patients were divided into three subgroups namely: severe LVSD for left ventricular ejection fraction 0.30, moderate LVSD for ejection fraction of 0.31–0.50, and mild LVSD for ejection fraction >0.50.
2.1 Statistical analysis
Operative mortality, defined as death in-hospital or within 30 days after surgery, was the primary outcome of interest.
Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 14.0 for Windows (SPSS Inc., 2005, Chicago, IL). Categorical variables are reported as percentages and compared between the groups with Pearson's chi-square test. The mean and standard deviation (±SD) are reported for continuous variables with symmetric distribution and compared using t tests, and for continuous variables with non-symmetric distribution, the median with 25th and 75th percentiles as interquartile range (IQR) are reported and compared between groups using the Mann–Whitney U test. Multivariate backward stepwise logistic regression models constructed with all preoperative and perioperative variables in Table 1
were utilised to identify the risk factors for operative mortality. First, a model was created for the entire study population, then separate models were constructed the elderly and young patients. A two-sided p
< 0.05 was considered significant.
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Table 1 The divergent clinical profiles of elderly (70 years) and young patients (<70 years) undergoing coronary and/or valve surgery.
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3. Results
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Of 6694 patients, 2616 were elderly and 4078 were young, with corresponding mean ages of 75 ± 4 and 60 ± 7 years. Table 1 highlights the contrasting characteristics of the two groups. More elderly patients were female, had advanced symptoms, controlled heart failure, and higher prevalence of comorbidities like renal failure, previous stroke, chronic obstructive airway disease and peripheral vascular disease. Severe (6% vs 5%) and moderate (22% vs 18%) LVSD were more prevalent in elderly patients (p
= 0.001). Surgical procedures also differed considerably between elderly and young patients. Isolated CABG was the predominant operation for both groups constituting 68% of all operations for the elderly and 81% for young patients. Aortic valve replacement (isolated and combined with CABG) was more common in elderly patients.
3.1 Postoperative morbidity and mortality
Elderly patients experienced more postoperative morbidity and mortality. Cardiovascular complications were the most common causes of postoperative morbidity (Table 2
). Haemodynamic support with inotrope infusions, with or without mechanical assistance occurred in 32% of elderly compared to 20% of young patients (p
< 0.0001). Mechanical support provided in 115 (4.3%) elderly and 123 (3%) young patients included: intra-aortic balloon pump in 112 (4.2%) elderly versus 121 (2.9%) young patients, and ventricular assist device in 5 (0.2%) versus 3 (0%) for elderly and young patients respectively. Early postoperative neurologic dysfunction (encephalopathy, reversible and permanent neurologic deficit) was observed twice as often in the elderly as in young patients (6% vs 3%, p
< 0.0001), with stroke accounting for 2.5% in the elderly and 1.2% in young patients.
The overall operative mortality was 4.4% (mean predicted EuroSCORE 6 ± 2) for elderly patients and 1.3% (median predicted EuroSCORE 3 ± 2) for young patients (p
< 0.0001). Elderly patients had greater procedure-specific operative death rates: 3.5% versus 1% (p
< 0.0001) for CABG, 3.2% versus 0.8% (p
= 0.02) for aortic valve replacement, 9.3% versus 3.2% (p
= 0.04) for mitral valve repair or replacement, and 6.4% versus 2.6% (p
= 0.08) for combined aortic valve replacement and CABG.
The risk factors for operative mortality for the entire study population were age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.05–1.10, p
< 0.0001), urgent operation (OR 1.69, 95% CI 1.14–2.51, p
= 0.009) emergency operation (OR 6.16, 95% CI 3.0–12.64, p
< 0.0001), previous stroke (OR 2.65, 95% CI 1.75–4.0, p
< 0.0001), controlled heart failure (OR 1.82, 95% CI 1.21–2.73, p
= 0.004), moderate LVSD (OR 1.69, 95% CI 1.10–2.59, p
= 0.02), severe LVSD (OR 4.88, 95% CI 2.96–8.02, p
< 0.0001), duration of cardiopulmonary bypass (OR 1.008, 95% CI 1.004–1.011, p
< .0001), mitral valve surgery (OR 2.71, 95% CI 1.35–4.45, p
< .005), and combined mitral valve surgery with CABG (OR 3.60, 95% CI 1.81–7.19, p
< .0001).
3.2 Influence of left ventricular systolic dysfunction on operative mortality
We investigated preoperative characteristics, operative variables, and surgical outcomes for patients with different degrees of LVSD (Table 3
). In general, with worsening LVSD, there was a steady decrease in the proportion of females and, increase in the prevalence of advanced symptoms, controlled heart failure, prior myocardial infarction, coronary artery disease, triple vessel disease, renal failure, and urgent/emergent operations. The incidences of severe symptoms and controlled heart failure however, were disproportionately higher in the elderly with moderate or mild LVSD and, left main stem disease and renal failure in elderly patients with severe LVSD, compared to their young counterparts. Urgent/emergent (non-elective) surgery was performed predominantly in the elderly for all LVSD subgroups; the difference between the proportions of elderly and young patients undergoing non-elective surgery was incremental from mild to severe LVSD.
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Table 3 Clinical profile and major complications in patients with different degrees of left ventricular dysfunction following cardiac surgery.
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Postoperative complication rates increased in direct proportion to the severity of LVSD, and occurred principally in elderly patients; mild LVSD 58% versus 42%, p
< 0.0001, moderate 62% versus 51%, p
< 0.0001 and severe 80% versus 70%, p
< 0.0001. Neurologic events occurred mostly in elderly patients in all subgroups. Operative mortality for CABG among elderly patients was substantially greater in all subgroups of LVSD: 2.3% versus 0.4%, p
= <0.0001, for mild LSV, 4.7% versus 2.3%, p
= 0.04 for moderate LVSD, and 13.5% versus 8.8%, p
= 0.01 for severe LVSD. Additional aortic valve replacement further increased mortality for elderly and young patients but significant difference between both age groups was observed only among those with severe LVSD.
3.3 Effect of cardiopulmonary bypass
There was no difference in the duration of cardiopulmonary bypass between the groups for similar operative procedures. The corresponding bypass times in minutes, for elderly and younger patients were; for CABG 59 min (IQR 46–73) versus 59 (IQR 46–74, p
= 0.35), for aortic valve replacement 62 min (IQR 55–75) versus 65 (IQR 56–76, p
= 0.32), for mitral valve repair/replacement 74 min (IQR 60–84) versus 72 (IQR 57–88, p
= 0.76), and for combined aortic valve replacement and CABG 88 min (IQR 74–105) versus 88 (IQR 74–110, p
= 0.73). Even then, there were eminent differences in the operative mortality between the two groups for similar types of operation. Also, the incidence of postoperative renal replacement therapy in preoperatively non-dialysis dependent patients was higher among the elderly (Table 2). The respective cumulative incidences in elderly patients was more than double that for young patients; (0.3% vs 1.2%, p
= 0.002) for short [60 min] CPB times and (0.9% vs 2.1%, p
= 0.004) for long [>60 min] CPB times, as depicted in Fig. 1
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Fig. 1. This figure relates the cumulative incidence for postoperative renal replacement therapy in preoperatively non-dialysis dependent elderly and young patients after primary coronary artery bypass and/or valve operation with the duration of cardiopulmonary bypass (60 and >60 min).
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The independent predictors of operative mortality in elderly and young patients are shown in Table 4
. Age (OR 1.09, 95% CI 1.03–1.15, p
= 0.002), duration of cardiopulmonary bypass (OR 1.01, 95% CI 1.0–1.02, p
< 0.0001) and mitral valve surgery (OR 2.45, 95% CI 1.05–5.74, p
= 0.04) were risk factors for elderly but not for young patients. Moderate LVSD (OR 3.01, 95% CI 1.45–6.26, p
= 0.003) and controlled heart failure (OR 2.61, 95% CI 1.26–5.38, p
= 0.01) were determinants of operative death for young patients but not for the elderly.
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Table 4 Risk factors for operative mortality in elderly and young patients undergoing coronary and/or valve surgery.
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4. Discussion
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Despite a general improvement in operative outcome of primary coronary and valve surgery [12], elderly patients still suffer a disproportionately higher operative morbidity and mortality compared to younger patients, due mostly to cardiovascular complications [13,14]. Age and other risk factors more prevalent in the elderly, contribute to these adverse outcomes. Like previous series [4,15], the present study found age to be a powerful predictor of operative mortality after cardiac surgery. In addition, and more significantly, this study demonstrates a differential impact of LVSD and CPB on operative mortality on account of age.
Moderate and severe LVSD are potent determinants of operative mortality, and regular features in contemporary risk scoring systems [16,17]. Our data however, shows that while severe LVSD (left ventricular ejection fraction 0.30) maintains a strong correlation with operative mortality in all age groups, the influence of moderate LVSD (left ventricular ejection fraction 0.31–0.50) was inconsistent for young and elderly patients. Moderate LVSD exhibited a significant correlation with operative mortality in young patients, but had no association with this outcome in the elderly. The predictive influence of heart failure was also diminished in the elderly. These findings are consistent with those of a large non-surgical study, the TRAndolapril Cardiac Evaluation (TRACE) study group [9] that examined the influence of age on the prognostic significance of left ventricular dysfunction and heart failure after myocardial infarction in 6676 patients. That study reported a decline in the relative importance of LVSD and heart failure with increasing age. Mehta et al. [4] also found an interaction between age and other risk factors in their study of 31,688 patients who underwent mitral valve surgery. Our finding has important implications for the surgical management of elderly patients. The diminished influence, in the elderly, of risk factors that exact significant effect on operative outcome for young patients suggests that with advanced age the impact of risk factors may change; a concept not captured by contemporary risk scoring systems. A similar association with advanced age has been reported for gender, another factor used for risk stratification [5]. It is important to note that contemporary risk stratification systems [17,18] are based on data collected from relatively young patients. For example, the mean age for the EuroSCORE dataset was 62.5 years and only 10% of patients were 75 years or older [19]. The accuracy of these risk assessment methods in elderly patients is controversial. As the number of elderly patients undergoing cardiac surgery steadily increases, a re-evaluation of risk assessment for this patient population is warranted.
Attention has been drawn to the damaging effect of CPB in general [20] but the clinical advantage of avoiding CPB has not been established for coronary artery surgery [21]; consequently the off-pump technique is used selectively in most centres [22,23]. It is worthy of note therefore, that the present study revealed an age-related disparity in the predictive risk of CPB. It appears that elderly patients do not tolerate CPB as well as young patients, which probably explains why the duration of CPB had a direct incremental effect on the risk of operative mortality in the elderly but had no adverse impact in young patients. The data of te Velthuis et al. [11] demonstrated a difference in response to CPB between elderly and young patients; biochemically the elderly had marked endotoxaemia and higher TNF 
concentrations compared to young patients, and haemodynamically, the pulmonary capillary wedge pressures and mean pulmonary artery pressure were higher and the stroke work index lower, in the elderly. Cardiopulmonary bypass therefore, contributes to impaired left ventricular performance, which accounts for the most frequent postoperative morbidity and mortality. Other series have identified CPB and age as risk factors for postoperative renal failure [24], and our study reveals an exponential increase in the incidence of postoperative renal replacement therapy in preoperatively non-dialysis dependent elderly patients, with increase in CPB duration. It has been suggested that a more biocompatible bypass system for the elderly which is associated with less adverse biochemical response [25] may improve clinical outcomes.
The inherent limitations of a retrospective study design apply to this series. We used 70 years as a cut-off for dividing the study population into two groups to provide adequate sample size for the elderly group so that a meaningful comparison could be performed. A similar comparison using 75 years resulted in the same findings but there was major disparity in the numbers between the groups (elderly to young ratio of 1:5). The interaction of age with LVSD and CPB time was not investigated in this study as we could not confidently control for potential major confounders arising from such a methodology in a retrospective study, with our dataset. While that would have added a different perspective to this report, the findings of this large study are relevant to current practice.
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5. Conclusion
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Age is a powerful risk factor and largely accounts for the difference in operative mortality between elderly and young patients. However, there are differences in the impact of other risk factors between these two groups of patients that contribute to the higher operative risk in the elderly. Our data demonstrated that duration of cardiopulmonary bypass had a strong association with operative death for the elderly but not for young patients. Whereas moderate left ventricular dysfunction (ejection fraction 0.31–0.50) and heart failure were influential in young patients, their impact was tempered in the elderly. Further studies are warranted to determine the reliability of current methods of risk stratification in elderly patients, and the role of biocompatible cardiopulmonary bypass systems in this growing surgical population.
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Abstract
1. Introduction
