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Ann Thorac Surg 1998;66:1632-1639
© 1998 The Society of Thoracic Surgeons
a Divisions of Cardiology and Cardiothoracic Surgery, Emory University, Atlanta, Georgia, USA
Accepted for publication May 14, 1998.
Address reprint requests to Dr Craver, Division of Cardiothoracic Surgery, Emory Clinic, Inc, 1365 Clifton Rd, NE, Atlanta, GA 30322
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Abstract |
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Methods. Between 1981 and 1995, 156 (1.3%) patients with an EF less than 0.25 (group 1), 588 (5%) patients with an EF of 0.25 to 0.34 (group 2), 2,438 (20.6%) patients with an EF of 0.35 to 0.49 (group 3), and 8,648 (73.1%) patients with an EF equal to or greater than 0.50 (group 4) underwent coronary artery bypass grafting. The EFs were determined by uniplanar or biplanar left ventriculography. For each group, the clinical and angiographic characteristics and the operative and outcome data were compared. Survival curves were derived and compared for each group. Correlates of angina, and of early (30-day) and long-term mortality, for all groups were analyzed.
Results. For all groups the mean age was approximately 60 ± 10 years. Group 1 had the highest percentage of patients who were men (88%), had congestive heart failure (34%), had hypertension (53%), and had left main coronary artery disease (24%). Groups 1 through 3, compared with group 4, had a lower percentage of complete revascularization (p < 0.0001), a lower percentage of internal mammary artery grafts (p < 0.0001), and a greater use of intraaortic balloon pump (p < 0.0001), but had similar cross-clamp and cardiopulmonary bypass times, number of grafts, incidences of myocardial infarction, and stroke. Hospital mortality for groups 1, 2, 3, and 4 was 3.8% (n = 6), 3.4% (n = 20), 3% (n = 72), and 1.6% (n = 134), respectively. Groups 1 through 3, compared with group 4, had similar incidences of angina during follow-up (31% to 40% versus 33%, respectively; p < 0.06). Survival was greatest for group 4 compared with groups 1 through 3 at 1, 5, and 10 years (p < 0.0001). Patients in group 1 had 1-, 5-, and 7-year survivals of 90%, 64%, and 49%. Multivariate correlates of early mortality were advanced age, female sex, decreased EF, hypertension, diabetes, and emergency operation. Multivariate correlates of long-term mortality included severity of preoperative angina class, congestive heart failure, number of diseased vessels, and incomplete revascularization. The strongest correlates of angina at follow-up were younger age, female sex, previous myocardial infarction, lower ejection fraction, and incomplete revascularization. The absence of an internal mammary artery graft did not predict the occurrence of angina or influence long-term survival.
Conclusions. In the long term there is a higher mortality in patients with sequentially decreased left ventricular function undergoing coronary artery bypass grafting, although more than 60% of patients with an EF less than 0.25 were alive and had good control of angina at 5 years despite having a higher percentage of risk factors, poorer functional status, and more complex coronary disease. Failure of symptom control and survival beyond 5 years appeared to be influenced by preexisting medical conditions and factors that affect the ability to completely revascularize the myocardium. These results suggest that in selected patients with ischemia and poor left ventricular function, coronary artery bypass grafting may preserve remaining viable myocardium, provide relief of symptoms, and offer survival greater than 60% at more than 5 years.
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Material and methods |
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TopFootnotesAbstractIntroductionMaterial and methodsResultsCommentReferences |
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The total population of patients available for analysis was 11,830. The patients were stratified into the following four common clinical categories of EF: EF less than 0.25 (group 1); EF of 0.25 to 0.34 (group 2); EF of 0.35 to 0.49 (group 3), and normal left ventricular function with an EF equal to or greater than 0.50 (group 4). The clinical and angiographic characteristics, operative data, hospital events, and survival were determined for each group. Follow-up during the postoperative period was 99% complete with a mean follow-up in years for survivors of the operation for groups 1 through 4 of 5.8 ± 3.7, 6.5 ± 4.2, 7.2 ± 4.4, and 8.1 ± 4.8, respectively.
Operative technique
Myocardial preservation for the period between 1981 and 1990 was primarily by intermittent oxygenated cold crystalloid cardioplegic solution [10]: Plasmalyte A, 1,000 mL; KCl, 25 mEq; dextrose (50%), 3 mL; NaHCO3, 20 mEq; and calcium gluconate (10%), 8.6 mL. Cardioplegia was delivered with a Bentley OxyHi delivery system, and the temperature (
8°C) was maintained through aluminum temperature coils placed in an ice bath. After the ascending aorta was cross-clamped, 1,000 mL of cardioplegia was administered into the aortic root at 150 to 300 mL/min and line pressures of 150 to 300 mm Hg. If electrical activity was still present, cardioplegia was continued until diastolic arrest was achieved. The heart was externally cooled with cold crytalloid ice-slush solution. Intermittent repeat doses of cardioplegia were then administered through the coronary sinus, aortic root, saphenous vein grafts, or a combination of these to maintain myocardial hypothermia. All distal anastomoses were performed first, and the majority of proximal anastomoses were performed under partial occlusion.
From 1990 to present, cold blood high-potassium and low-potassium cardioplegia with retrograde delivery has been used more liberally in patients with left ventricular dysfunction as described by Craver and associates [11]. Cardioplegia was delivered by a 4:1 blood to cardioplegia delivery system with the temperature maintained as either cold (8°C) or tepid (32°C) as specified by the surgeon. After aortic cross-clamping of the ascending aorta, the high-potassium blood cardioplegia (final concentration, 20 mEq/L) was infused into the root of the aorta at 100 to 350 mL/min and a pressure of 100 to 300 mm Hg until diastolic arrest was achieved. The low-potassium solution was then delivered into the coronary sinus through the transatrial retrograde coronary sinus catheter (Gundry retroplegia cannula; DLP, Inc, Grand Rapids, MI). Delivery was either intermittent cold or continuous tepid as dictated by the surgeon, and every effort was made to keep the coronary sinus pressure less than 40 mm Hg. Flow rate ranged from 40 to 250 mL/min. In some patients, the cardioplegia delivery was stopped for a short period (<10 minutes) to facilitate visualization of the distal coronary anastomosis, and in others cardioplegia was delivered through saphenous vein grafts between anastomoses. All distal anastomoses were performed first. The proximal anastomoses were performed under total aortic cross-clamping or partial occlusion at the surgeon’s discretion, with the majority done under partial occlusion.
Cardiopulmonary bypass with hypothermia to a systemic nasopharyngeal temperature between 28° and 32°C using single aortic and atrial cannulation techniques was routinely performed. Pump flows were maintained between 1.8 and 2.5 L · min-1 · m-2 as long as in-line venous saturation remained at 90% or greater. Perfusion pressures were maintained at 50 to 70 mm Hg. Initial heparinization was accomplished with 4.0 mg/kg and was supplemented as needed to maintain an activated clotting time greater than 300 seconds. Every effort was made to ensure complete revascularization. The use of the internal mammary artery (IMA) graft began in the mid-1980s, and it has been the conduit of choice for the past several years in all patients. Its use has not been influenced by the preoperative EF.
Statistical methods
All data were collected prospectively on standard forms and entered into a computerized database. All data were retrospectively analyzed with BMDP (BMDP Statistical Software, Inc, Los Angeles, CA) and Splus statistical software (Microsoft, Inc, Seattle, WA). All data were expressed as mean ± the standard deviation or as proportions. Survival was determined by Kaplan-Meier analysis with survival expressed as calculated probability ± the standard error of the mean. Differences in survival were determined by the Wilcoxon method. Correlates of survival were determined by Cox model analysis. Correlates of angina at follow-up were determined by stepwise logistic regression.
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Our study was able to show that although EF was a predictor of both early and late mortality, that even patients with sequentially decreased left ventricular EFs were able to have low incidences of in-hospital events and excellent long-term survival. In the past, perioperative mortality after CABG in patients with poor left ventricular function (EF < 0.25) has been reported to be between 10% and 37% [3, 5], but more recent reports indicate mortalities between 2.5% and 8% [6–8, 14], even in patients with a component of CHF [6, 7, 12–16]. In our study, 156 patients with a mean EF of 0.19, of whom 34% had CHF symptoms, had a hospital mortality of only 3.8% and had no perioperative MIs. We agree with other authors that the improved results have been attributed to advances in myocardial protection, surgical technique, and perioperative care [6, 7, 9, 10, 13, 14]. We have detailed in this and other reports [10, 11], and along with other investigators [8, 17], that blood cardioplegia and use of coronary sinus retroplegia are important components to myocardial preservation and resuscitation techniques in patients with advanced ventricular dysfunction. This report also showed that a nonelective operation correlated strongly with early, and to a lesser extent with late, survival. It is clear that patients with lower EFs should have attempts at hemodynamic stabilization before operation, and as our report emphasizes, this can be accomplished with increased perioperative use of the intraaortic balloon pump. Dietl and colleagues [18], Elefteriades and Kron [6], and Kaul and associates [8] each have demonstrated the safety and efficacy of the intraaortic balloon pump perioperatively in patients undergoing either elective or urgent CABG with severe left ventricular dysfunction. We believe these were important factors for the low incidences of perioperative MI and early deaths in the highest risk groups in our present study.
We believe an even more important factor in assuring a good outcome in these patients results from the ability to completely revascularize ischemic myocardium. Although identifying adequate target vessels on preoperative coronary angiograms have been emphasized [6, 7, 9, 14], this feature alone does not ensure the ability to revascularize all patients, especially those with the lowest EFs. In a study by Jones and Weintraub [19], the number of diseased vessels, lower EF, prior MIs, and hypertension were strong correlates of incomplete revascularization. In this study patients with an EF less than 0.25 had the highest percentage of these risk factors. These factors likely account for the significant decrease in complete revascularization in patients with sequentially decreased EFs. On the other hand, long-term survival can be achieved in patients with an EF less than 0.25 despite incomplete revascularization, although this survival advantage compared with patients with EFs greater than 0.25 is lost beyond 5 years (Fig 1). This is likely a result of many factors, but may in part be related to the ability to revascularize the left anterior descending coronary artery or multiple vessels less frequently in patients with an EF less than 0.25 [19]. This report also confirms earlier data by Jones and Weintraub [19] that show that the type of conduit is less important on survival than on the ability to completely revascularize the myocardium. It remains our opinion that supplying at least one graft to each of the three major myocardial territories, especially in patients with left ventricular dysfunction as a result of ischemia, is of greatest prognostic significance.
Although other reports have also shown 5-year survivals between 60% and 80% after CABG in patients with severe left ventricular dysfunction [6, 8, 14], our study shows that beyond 7 years there is a significant late mortality in these patients. Several studies have shown that these patients die because of progressive CHF symptoms, and to a lesser extent events related to ischemia or sudden death [3, 4, 6, 8, 14]. Kaul and associates [8], Mickelborough and coworkers [14], and Elefteriades and Kron [6] all have emphasized the need to identify preoperative predictors that limit long-term survival in these high-risk patients. Through multivariate analysis we identified several factors that correlated with poor survival. The clinical factors that correlated with early or late death included older age, female sex, diabetes, severity of angina class, hypertension, and CHF. The implication from these results is not that multiple risk factors should necessarily exclude patients from CABG, but that careful perioperative and long-term postoperative management of these factors may improve longevity.
It was not surprising that some of the correlates with poor survival were also correlates with angina recurrence at follow-up. The findings that the presence of preoperative diabetes, hypertension, CHF, and previous MI were predictors of angina recurrence reemphasize the need for management of these factors after CABG irrespective of EF. Not surprising was that the younger patients had risk of angina in follow-up. Perhaps these patients should be particularly targeted for long-term management. In addition, although it has been emphasized that the presence or severity of preoperative angina in patients with low EFs predicts a good result after CABG, our results have demonstrated that the severity of preoperative anginal symptoms was a strong predictor of angina at follow-up for this subgroup. This result may be in part explained by the fact that incomplete revascularization and lower EFs were strong correlates of angina at follow-up, regardless of the number of diseased vessels. Although the absence of an IMA graft did not correlate with angina at follow-up or impact survival, its more prevalent use in later years may account for the inability to demonstrate a protective benefit. These results further help identify preoperative risk factors that can be addressed after CABG that may further improve control of angina in the long term.
The ultimate question to be addressed is how to select which patients with severe CAD and low EFs will have the best long-term outcomes. Because there is a direct correlation between the amount of viable myocardium at risk and the number and quality of arteries supplying the area [19], and not the presence or degree of angina, it becomes important to be able to predict which patients with lower EFs will benefit long-term after CABG. Rahimtoola [20] has also emphasized that in patients with chronically ischemic or hibernating myocardium, depressed EFs or severe left ventricular dysfunction may be a protective mechanism as a means of reducing oxygen demand and limiting ischemia and cellular necrosis. He therefore further emphasizes that although angina may be a prevalent feature, minimal or lack of anginal symptoms neither precluded or portended unsuccessful outcome after CABG [20]. This rationale becomes important, because many patients may have congestive symptoms as a predominant manifestation of their ischemic myocardium [6, 8, 14], as evidenced by the presence of CHF in more than 30% of patients in our study with EFs less than 0.25. In patients with CHF symptoms as a result of ischemic myocardium, there is likely overlap in the presence of viable or fibrosed myocardium [20, 21]. Relief of congestive failure and stabilization or improvement of left ventricular EF has been observed after CABG in patients with ischemic cardiomyopathy, but with less predictability than relief from angina [6–9, 14].
A major limitation of the use of decreased EF as an indicator of impaired left ventricular function is the inability of this variable to differentiate myocardium that is depressed because of reversible myocardial ischemia (or hibernating myocardium) from myocardium depressed by fibrosis from previous infarction. Although viability studies such as dobutamine echocardiography [22], thallium-201 imaging [23], and positron emission tomography [22, 24] have been shown to identify reversible or viable ischemic myocardium in patients with severe left ventricular dysfunction and have had a larger role in evaluating candidates for heart transplantation, most surgical reports have used the results of uniplanar or biplanar left ventriculography to assess the status of the left ventricle before CABG. However, reports by Chan and colleagues [25], Kaul and associates [8], and Louie and coworkers [9] have demonstrated good long-term relief of symptoms and survival after CABG in patients with EF less than 0.30 who demonstrated large reversible defects on preoperative stress thallium-201 scintigraphy or myocardial viability on positron emission tomographic scans. Because our study covered such a large time interval in which viability studies were not available, we did not evaluate the role of these studies in predicting operability based on viable myocardium. Nonetheless, patients with an EF less than 0.25, of whom 60% had preoperative class III–IV angina and more than one third had CHF symptoms, were able to have greater than 60% control of angina and survival at 5 years suggesting preservation of viable myocardium. In recent years, when patients with severe left ventricular function as a result of ischemic myocardium are referred for CABG, if their target vessels are in question, or there is a chance for incomplete revascularization, or angina symptoms are nor prevalent, we will refer the patient for a viability study as dictated by our heart failure cardiologists. Over time, we will have to determine whether studies of myocardial viability help select patients who will benefit long term after surgical revascularization.
The results from our study show that despite having a higher percentage of risk factors, poorer functional status, and more complex coronary anatomy, patients with compromised left ventricular function have good in-hospital outcomes. Although long term there is a higher mortality in patients with sequentially decreased EFs, more than 60% of patients with an EF less than 0.25 were alive after 5 years and had good control of angina. Failures in symptom control and survival beyond 5 years appear to be influenced by preoperative or preexisting medical conditions and factors that affect the ability to completely revascularize the myocardium. These results suggest that in selected patients with advanced left ventricular function caused by ischemic myocardium, CABG may preserve remaining viable myocardium, provide relief of symptoms, and offer surival greater than 60% after 5 years.
The implications from this study are that long-term control of angina and survival may be improved by selection and management strategies addressing specific clinical and operative factors that predicted these events late at follow-up. Selected patients referred for CABG with ischemic cardiomyopathy may be similarly evaluated as patients referred for heart transplantation to establish whether coronary revascularization is a viable initial treatment option. In evaluating these often overlapping patient groups, there will likely be a number of heart transplantation candidates who can benefit from CABG, thereby potentially reducing the long recipient waiting lists. Therefore, in cooperation with cardiologists who manage patients with left ventricular dysfunction, it becomes important to establish selection and management strategies that further improve long-term successes after CABG in this growing group of high-risk patients.
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G. B. Luciani, G. Montalbano, G. Casali, and A. Mazzucco Predicting long-term functional results after myocardial revascularization in ischemic cardiomyopathy J. Thorac. Cardiovasc. Surg., September 1, 2000; 120(3): 478 - 489. [Abstract] [Full Text] [PDF]
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