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Eur J Cardiothorac Surg 2007;32:623-628. doi:10.1016/j.ejcts.2007.07.004
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

The impact of symptom severity on cardiac reoperative risk: early referral and reoperation is warranted

Cardiothoracic Centre, Castle Hill Hospital, Cottingham, East Yorkshire HU15 6JQ, United Kingdom

Received 19 March 2007; received in revised form 2 July 2007; accepted 3 July 2007.

^_* Corresponding author. Tel.: +44 1482 623256; fax: +44 1482 623257. (Email: dngaage{at}yahoo.com).

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Result 4. Discussion 5. Conclusion References

 
Background: Operative mortality is comparatively higher for coronary artery bypass grafting (CABG) or valve reoperations. Studies of reoperative risk have focussed on surgical techniques. We sought to determine the risk and predictors of poor outcome in current practice, and the influence of preoperative symptoms. Method: For every redo patient (n = 289), we selected the best-matched pair of patients who underwent a primary operation (n = 578) between 1998 and 2006. Matching variables were age, gender, left ventricular ejection fraction (LVEF) and type of operation. Poor outcome was defined as operative mortality or major morbidity. Result: Median age was 68 (interquartile range 62–73) years and 28% were female for both groups. Severe symptoms and cardiac morbidity dominated the presentation of redo patients. CABG (53%), valve repair/replacement (34%) and combined CABG and valve (12%) were performed with overall operative mortality of 6.6% (median additive EuroScore 7.0) for redo versus 1.6% (median additive EuroScore 4.0) for primary groups (p < .0001). Whereas no significant difference was observed between primary (1.6%) and redo CABG (3.9%, p = .19), valve reoperations had higher operative mortality (9.6% vs 1.5%, p < .0001). Major complications occurred more frequently after redo valve compared to primary valve operations (28% vs 14%, p = .001). Reoperation (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.66–2.42, p = .48) was not a predictor of major adverse event after CABG or valve surgery. Determinants of poor outcome after valve reoperations were New York Heart Association class III/IV (OR 6.86, 95% CI 2.29–12.11, p = .03), duration of extracorporeal circulation (OR 1.17, 95% CI 1.02–1.35, p = .03) and mitral valve replacement (OR 4.07, 95% CI 1.83–36.01, p = .04). The predictors of major adverse events after redo CABG were congestive heart failure (OR 1.85, 95% CI 1.04–8.98, p = .006) chronic obstructive pulmonary disease (OR 17.5, 95% CI 1.87–35.21, p = .05) and interval from prior surgery (OR 1.37, 95% CI 1.09–1.92, p = .01). Conclusion: In the current era, redo CABG is nearly as safe as the primary operation. A valve reoperation, on the contrary, is higher risk due, partly, to severe symptoms at presentation. Patients should be referred and operated on early before they develop severe symptoms.

Key Words: Reoperation • CABG • Valve replacement/repair • Operative mortality/morbidity • Severe symptom

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Result 4. Discussion 5. Conclusion References

 
The operative mortality associated with redo CABG or heart valve repair/replacement exceeds the rates for the corresponding primary operation [1–4]. In order to reduce this risk, several technical strategies have evolved with some success [5–8]. Recent studies have excluded reoperation as a risk factor for operative mortality; instead patient characteristics and comorbidities have been identified as determinants of operative mortality [9]. Often, however, only the operative mortality is reported to the exclusion of potentially fatal and debilitating complications that can mar the outcome of reoperations. Hence the incidences of these complications and their risk factors have not been clearly defined. Also, data about the influence of preoperative symptoms are lacking. We therefore sought to (1) identify the factors that determine major adverse postoperative events (major operative morbidity or mortality) after reoperative coronary artery bypass grafting (CABG) or heart valve repair/replacement, and (2) assess the impact of symptom severity on the outcome of cardiac reoperations. In order to achieve these objectives we compared the early outcome of cardiac reoperations to the corresponding primary procedures between matched cohorts.

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Result 4. Discussion 5. Conclusion References

 
2.1 Study population
The medical and ethics committee approved the use of patient data for this study. Prospectively collected data of 6704 patients who underwent primary cardiac operation and 690 who had repeat cardiac surgery between December 1998 and August 2006 were analysed. We identified patients who underwent reoperative on-pump CABG (n = 380), valve repair/replacement (n = 175) and combined CABG and valve operation (n = 107). All those who had previous aortic surgery and correction of congenital cardiac abnormality in childhood were excluded, as were those operated for infective endocarditis. Of 315 eligible redo patients, we found best matched pairs for 289 on the basis of age, gender, left ventricular systolic function and type of surgical procedure among patients who underwent primary cardiac operation, using the Greedy method [10]. Demographic information, clinical symptoms, comorbidities, operative and postoperative details were retrieved from the database and supplemented with chart review.

2.2 Surgical technique
Surgical access was by median sternotomy in all the study patients. Cardiopulmonary bypass was established by intrathoracic cannulation in all primary operations and in the vast majority of redo procedures. Planned femoral cannulation was used in some redo patients. Antegrade blood cardioplegia or cross-clamp fibrillation were the predominant methods of myocardial protection in primary operations, while antegrade and retrograde blood cardioplegia was used in the reoperations.

2.3 Statistical analysis
The primary end point was major adverse postoperative event; defined as death or a potentially fatal or debilitating complication such as postoperative myocardial infarction, renal failure requiring renal replacement therapy in the form of haemofiltration or haemodialysis, stroke, mediastinitis, septicaemia, massive gastrointestinal bleeding requiring endoscopy with or without injection or cauterisation, or acute abdomen. Secondary end points were postoperative length of stay in the intensive care unit and postoperative hospital stay.

Categorical variables are described as percentages and compared between groups with the chi-square test, while continuous variables are reported as median with the 25th to 75th percentiles referred to as interquartile range (IQR), and compared between groups using the Mann–Whitney U test. Redo and primary operation groups were compared over the study period, and specific operative procedures; CABG (redo vs primary) and valve repair/replacement (redo vs primary) were analysed separately. Sub analyses were performed to elucidate trends and track changes within each group, and between groups from early (1998–2001) to late (2002–2006) study periods. The predictors of major adverse postoperative events were identified using multivariate Logistic regression model constructed with all the variables listed in Table 1 , perioperative and operative details in Table 2 and era of surgery. Statistical significance was set at p < .05. The Statistical Package for the Social Sciences (SPSS) version 14.0 for windows, (SPSS Inc. 2005, Chicago, IL) was utilised for the analysis.

	3. Result

Top Abstract 1. Introduction 2. Materials and methods 3. Result 4. Discussion 5. Conclusion References

We further investigated differences in clinical presentation between the groups over two eras of the study period (Table 2). In the early era from 1998 to 2002, 56% of the patients undergoing redo operation had severe symptoms (angina class III/IV or NYHA functional class III/IV) compared to 36% of those undergoing primary operation (p < .0001). In the late era from 2002 to 2006, we observed a general decrease in the prevalence of severe symptoms, but more redo patients still had severe symptoms at the time of surgery. The prevalence of congestive heart failure in redo patients remained unchanged for early and late periods (59% vs 54%, p = .48) but decreased significantly in the primary group (45% vs 34%, p = .01).

3.2 Major adverse postoperative events
The overall operative mortality was 6.6% (19 patients, median additive EuroScore 7.0) for redo versus 1.6% (nine patients, median additive EuroScore 4.0) for primary group (p < .0001). The mortality in the early era was 2.2% (eight patients) for primary operations and 8.5% (12 patients, p = .003) for reoperations. In the late era, this decreased to 0.5% (one patient) and 4.8% (seven patients, p = .009) for primary and redo operations, respectively. This decline in operative mortality for primary operations was significant but was not statistically significant for reoperations (see Table 2).

Major postoperative morbidity was observed more frequently in the redo group due to higher rates of gastrointestinal complications and postoperative acute renal failure, as shown in Table 3 . Gastrointestinal complications included gastrointestinal bleeding and acute abdomen. The combined end point of operative mortality and major morbidity (major adverse postoperative event) occurred more frequently among the redo group (20% vs 13%, p = .008). The predictors of major adverse events for the whole study population were age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.01–1.08, p = .02), NYHA class III/IV (OR 1.94, 95% CI 1.03–3.66, p = .04), chronic obstructive pulmonary disease (OR 2.92, 95% CI 1.59–5.40, p = .001), preoperative renal failure (OR 3.61, 95% CI 1.11–11.68, p = .03), cardiogenic shock (OR 7.51, 95% CI 1.47–38.43, p = .02), duration of extracorporeal circulation (OR 1.03, 95% CI 1.02–1.05, p < .0001) and combined CABG and valve operation (OR 5.46, 95% CI 1.20–24.79, p = .03). Surgery in the late era (OR 0.48, 95% CI 0.28–0.82, p = .007) was associated with a reduction in the risk. Reoperation (OR 1.26, 95% CI 0.66–2.42, p = .48) however, was not a risk factor for a major adverse event.

3.2.1 CABG
The operative death rate was 1.6% (five patients) for primary CABG (additive EuroScore 3, IQR 2–5) and 3.9% (six patients, p = .19) for reoperation (additive EuroScore 6, IQR 4–7). The operative mortality was stable through the early and late eras for both primary (1.8% vs 1.2%, p = 1.00) and redo CABG (4.8% vs 2.8%, p = .69) operations. Similarly, the incidence rates of major adverse postoperative events were comparable for primary and redo CABG (11% vs 12%, p = .76), and did not differ significantly between the two eras (see Table 2).

The predictors of major adverse postoperative event after CABG were age (OR 1.07, 95% CI 1.01–1.13, p = .02), pre-existing atrial fibrillation (OR 4.92, 95% CI 1.60–15.10, p = .005), duration of extracorporeal circulation (OR 1.04, 95% CI 1.01–1.07, p = .002) and concomitant valve operation (OR 3.82, 95% CI 1.39–10.52, p = .03). Reoperation (OR 1.20, 95% CI 0.4–3.56, p = .75) was not a determining factor. After reoperation, congestive heart failure (OR 1.85 95% CI 1.04–8.98, p = .006), chronic pulmonary disease (OR 17.5 95% CI 1.87–35.21, p = .05) and the interval from prior surgery (OR 1.37 95% CI 1.09–1.92, p = .01) were the risk factors for major adverse outcome.

3.2.2 Valve operation
Operative mortality for primary isolated valve surgery was 2.0% (two patients, additive EuroScore 6, IQR 4–7) compared to 6.5% (13 patients, additive EuroScore 9, IQR 7–10) for reoperations (p = .005). Amongst valve operations, aortic valve replacement was associated with mortality rates of 0.7% for primary (additive EuroScore 6, IQR 5–7) and 6.9% for redo (additive EuroScore 9, IQR 8–11, p = .02), while mitral valve procedures had death rates of 2.7% (primary, additive EuroScore 6, IQR 4–7) and 13% (redo, additive EuroScore 9, IQR 8–12, p = .02). The trend in operative mortality over the study period showed some decline from early to late era, for both primary (2.9% to 0%, p = .12) and redo valve operations (13.6% to 6.6%, p = .24) but these did not reach statistical significance. Unlike CABG, there was a substantial difference in the operative mortality between primary and redo valve operations in both early (p = .007) and late eras (p = .007), as depicted in Table 2.

Compared to primary operations, valve reoperations were associated with higher major adverse postoperative event rates (28% vs 14%, p = .001). This was consistent for the two eras as well.

The determinants of major adverse postoperative events after valve operation were preoperative renal failure (OR 12.14, 95% CI 1.13–130.66, p = .04), left ventricular ejection fraction less than 30% (OR 1.12, 95% CI 1.01–8.17, p = .03), pre-existing atrial fibrillation (OR 11.44, 95% CI 2.35–55.60, p = .003), additional CABG (OR 9.62, 95% CI 2.00–46.21, p = .005), and duration of extracorporeal circulation (OR 1.03, 95% CI 1.01–1.05, p = .004). Surgery in the late era had a favourable effect on operative outcome (OR 0.40, 95% CI 0.18–0.92, p = .03). Reoperation (OR 1.49, 95% CI 0.61–3.65, p = .39) was not a predictive factor. The determinants of major adverse outcome after redo valve repair/replacement were NYHA class III/IV (OR 6.86, 95% CI 2.29–12.11, p = .03), duration of extracorporeal circulation (OR 1.17, 95% CI 1.02–1.35, p = .03) and mitral valve replacement (OR 4.07, 95% CI 1.83–36.01, p = .04).

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Result 4. Discussion 5. Conclusion References

 
Given that redo patients more often have severe cardiovascular symptoms and higher cardiac morbidity at the time of surgery, the operative mortality and morbidity associated with reoperation is higher in comparison to primary operation. This is consistent with the findings of other studies [4,9]. However, there is a decline in the operative mortality of reoperations which tracks improvement in the results of primary cardiac operations. Some series have shown indirect improvement in the results of reoperation in an era where the operative risks of cardiac patients continue to increase. Like our study, Yau et al. [11] reported a stable operative mortality over a 15-year period in 1230 patients undergoing repeat CABG, in spite of worsening risk profile.

The present study investigates the incidence of major postoperative morbidity, in addition to operative mortality (major adverse postoperative event) after cardiac reoperation, and thereby enables a fairly comprehensive evaluation of the risk of reoperation. A notable finding of this study is the comparatively higher rate of major postoperative morbidity after valve reoperations. Patients undergoing repeat valve replacement or repair experienced higher rates of potentially fatal or debilitating complications like acute abdomen, gastrointestinal bleeding and acute renal failure requiring renal replacement therapy. Whereas a high prevalence of preoperative renal function impairment might have predisposed redo patients to a higher incidence of postoperative renal failure, this was not the case with gastrointestinal complications. Despite equivalence in the prevalence of gastrointestinal disorders between the two groups preoperatively, there was a significantly higher rate of gastrointestinal complications after reoperations.

4.1 Paradigm shift
Improvement in the outcome of reoperative cardiac surgery has resulted from progress in perioperative care and advances in surgical techniques. Notably, various technical strategies described to reduce the risk of reoperation have focused on techniques of resternotomy [6,12,13], alternative surgical access including minimally invasive incisions and thoracotomy [8,14–16], myocardial protection [5,17,18] and avoiding cardiopulmonary bypass [19–21]. Different combinations of these techniques [7,22] have also been associated with good outcomes. Consequently, reoperation itself is no longer a risk factor for poor outcome as our study shows. For both CABG and valve surgery, reoperation did not have a statistically significant effect on major adverse postoperative event. Similarly, Sabik et al. [9] and Darvierwala et al. [23] and their associates did not identify reoperation as a risk factor for operative mortality after redo CABG.

It is noteworthy however, that the surrogates of advanced cardiac disease, rather than patient characteristics, exhibited significant influence on the outcome of cardiac reoperations in this matched cohort study. Congestive heart failure and the interval between operations in patients undergoing redo CABG, and severe dyspnoea in those having valve reoperation, precluded a favourable outcome of reoperation. Masri et al. [3] and O’Brien et al. [24] reported similar findings. This emphasises the importance of early, rather than late reoperative intervention, and begs the question of the optimal timing of CABG or valve reoperations. Not uncommonly, patients with recurrent symptoms after prior cardiac surgery are managed conservatively until severe symptoms dominate the presentation, and limit the patient functionally. This is highlighted by the consistent predominance of severe symptoms among redo patients through the two eras of the study period. Since symptoms often trail physiologic and morphologic changes in valvular heart disease, the presence of severe symptoms generally indicate advanced valvular disease associated with a decompensated and failing heart. This engenders a vicious cycle of poor operative outcome justifying protracted non-surgical treatment and hence delayed surgery. Even though it may be problematic to define the criteria for reoperative coronary or valvular heart surgery as other than failed medical treatment, surgical intervention should be considered early in recurrent disease. The association of interval between operations and congestive heart failure with major adverse postoperative events in patients with progressive coronary artery disease requiring reoperation is indicative of the poor prognostic influence of delaying redo CABG. The findings of our study strongly suggest early referral and reoperation of patients, certainly before symptoms become severe. More so, since reoperations are relatively safe in current practice, this treatment modality should not be deferred until the benefit of surgery is compromised by disease progression and severity.

4.2 Study limitation
The retrospective nature of the study has its inherent drawbacks. As data was not specifically acquired for this study, some variables such as patency of previous grafts was not available for most of the patients. However, none of the operative deaths were related to injury to a patent graft at surgery. The predictors of adverse outcome were not identified separately for aortic and mitral valve reoperations because of the small number of events in the patients undergoing the specific operations. While we accept that aortic and mitral valve reoperations provide different surgical challenges, the preoperative status of the patient can have a profound influence on the surgical outcome. Advanced aortic and mitral valve disease would both present with severe symptoms, which is identified in this study as an independent predictor of major adverse postoperative event.

	5. Conclusion

Top Abstract 1. Introduction 2. Materials and methods 3. Result 4. Discussion 5. Conclusion References

 
The risk of reoperative CABG or valve repair/replacement has declined; in fact, redo CABG can be performed in the current era with the operative risk comparable to the primary operation. The risk of reoperative valve surgery, however, is still significantly higher than primary valve repair/replacement. The majority of patients present with severe symptoms at reoperation, which is a predictor of major adverse postoperative event, including death, after valve reoperation. Surgery should be considered early in the management of recurrent or progressive cardiac disease before severe symptoms develop and compromise the outcome of reoperation.

	References

Top Abstract 1. Introduction 2. Materials and methods 3. Result 4. Discussion 5. Conclusion References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Dumbor L. Ngaage Michael E. Cowen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ngaage, D. L. Articles by Cale, A. R. Search for Related Content PubMed PubMed Citation Articles by Ngaage, D. L. Articles by Cale, A. R. Related Collections Cardiac - other Coronary disease Valve disease