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Ann Thorac Surg 2003;75:1406-1412
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Determinants of mid- and long-term results in patients after surgical revascularization for ischemic cardiomyopathy

^a Department of Thoracic and Cardiovascular Surgery, Heart Center of Northrhine-Westfalia, University Hospital Ruhr-University Bochum, Bad Oeynhausen, Germany

Accepted for publication November 12, 2002.

^* Address reprint requests to Dr Kleikamp, Klinik für Thorax- und Kardiovaskularchirurgie, Herzzentrum Nordrhein-Westfalen, Universitätsklinik Ruhr-Universität Bochum, Georgstr 11, 32545 Bad Oeynhausen, Germany
e-mail: gkleikamp{at}hdz-nrw.de

	Abstract

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BACKGROUND: The revascularization of patients suffering from ischemic cardiomyopathy is possible with acceptable perioperative mortality and morbidity. Many publications have discussed the problem of predicting myocardial viability, whereas the quality of the peripheral coronary vessels has been focused on less frequently.

METHODS: We studied 908 consecutive patients with ischemic cardiomyopathy revascularized between January 1, 1988 and April 30, 2000. Death, recurrent heart failure, hospitalization due to cardiac causes, ventricular assist device implantation, heart transplantation, and ventricular arrhythmias were defined as adverse events. To analyze the importance of pre- and perioperative variables (state of the coronary arteries, myocardial viability, complete vs incomplete revascularization, urgency of the operation, previous operations, gender, diabetes, preoperative New York Heart Association class, age, number of grafts, and ischemic time), a proportional hazards model was used.

RESULTS: The most important predictors of short- and long-term event-free survival were the quality of the coronary arteries, followed by myocardial viability, complete revascularization, number of bypass grafts, and an elective operation.

CONCLUSIONS: The coronary vascular system can be described by means of a simple scoring system. A good or at least moderate coronary artery perfusing an area of dysfunctional yet viable myocardium is the main predictor of a successful perioperative course and an event-free survival. Patients with a poor coronary vasculature regardless of myocardial viability should not be considered suitable for revascularization.

	Introduction

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This article has been selected for the open discussion forum on the CTSNet Web site: http://www.ctsnet.org/discuss

 

The natural history of patients suffering from advanced coronary artery disease with severe impairment of left ventricular function resulting in congestive heart failure is even worse than that of other cardiomyopathies [1]. Orthotopic heart transplantation and myocardial revascularization are the two most important surgical procedures for patients with ischemic cardiomyopathy [2–4].

Other surgical options have evolved over recent years for special indications, for exapmle, implantation of ventricular assist devices (VAD) in patients with acute deterioration of cardiac function [5] and cardioverter-defibrillators in patients suffering from ventricular arrythmias. In selected patients with heart failure and intraventricular conduction delay, the implantation of a biventricular pacing device may improve the cardiac function [6]. The aim of the present study was to define the early and late functional results after revascularization in patients with ischemic cardiomyopathy and to identify variables predictive of a favorable outcome in a large single-center series.

	Material and methods

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Between January 1, 1988 and April 30, 2000, 25,887 patients underwent surgical revascularization at our institution. Patients suffering from ischemic cardiomyopathy defined as global (left ventricular ejection fraction < 30%) and regional wall motion abnormalities were entered prospectively into a computerized database (Apple Power PC [Apple Computers Power PC, Cupertino, CA]; Statview statistical package [Abacus Concept, Inc, Berkeley, CA]), as were their follow-up data. Exclusion criteria for the present study included operable ventricular aneurysms and significant valvular heart disease to ensure hemodynamic comparability. Nine hundred and eight consecutive patients (3.5%) underwent surgical revascularization. Seven hundred and ninety-seven (87.8%) of the patients were men and 111 were women (12.2%). The mean age was 60.1 ± 9.4 years (range, 29 to 78 years). We compared the pre- and perioperative data of patients with an uneventful course with those suffering from adverse events. Death, postoperative recurrent heart failure, hospitalization because of cardiac causes, ventricular assist device (VAD) implantation, heart transplantation, and ventricular arrhythmias were defined as adverse events. To analyze the importance of pre- and perioperative variables, a proportional hazards model (Cox) was used. Furthermore, some data were analyzed using Kaplan-Meier actuarial survival analysis. Differences over time were analyzed by means of a log-rank test. The cardiac history was recorded, including the severity of angina pectoris (Canadian Cardiovascular Society classification), congestive heart failure (New York Heart Association [NYHA] classification), and previous interventional or surgical cardiac revascularization.

Hibernating myocardium was assumed when the metabolic scans (fluoro-18-desoxyglucose) demonstrated preserved metabolism and the perfusion scans (N-13-ammonia) showed diminished perfusion in a myocardial segment. The segments targeted for revascularization were judged either completely viable, or partially or totally scarred. Cardiac catheterization results, including degree and distribution of coronary artery stenoses, status of the peripheral coronary vasculature, approximate size of the coronary vessels, left ventricular ejection fraction, and regional wall motion, were recorded. The left ventricle was diveded into six areas (anterior wall basal, anterior wall apical, posterior wall basal, posterior wall apical, septum, and lateral wall), and the results of the coronary angiograms and scintigraphic and echocardiographic examinations were related to these areas and compared.

The coronary angiograms (1,246 from 908 patients) were examined by at least two experienced cardiac surgeons. The quality of the coronary vascular system was classified into three categories: 1) good (coronary vessels with relevant [> 70%] stenoses or obstruction in the proximal segment without distal stenoses, diameter more than 2 mm); 2) fair (same as first category, but with nonsignificant distal stenoses, diameter 1.5 to 2 mm); and 3) poor (vessels with proximal and distal stenoses, diameter less than 1.5 mm). The quality of the coronary vascular system was judged concerning all stenosed or occluded arteries. The overall categorization was made according to the majority of arteries; in cases with equal numbers of arteries in two categories, the better was choosen. The priority of each operation was graded according to the Society of Thoracic Surgeons classification. Completeness of revascularization was judged postoperatively, independently by two surgeons; complete revascularization was defined as bypassing all significantly stenosed or occluded vessels. If this was not achieved (mainly due to technical reasons), the revascularization was considered incomplete. The operative technique did not vary during the study intervall with respect to myocardial protection, perfusion management, and performance of the distal and proximal anastomoses. Myocardial protection consisted of intermittent aortic cross-clamping and mild hypothermia for performance of the distal anastomoses. The proximal anastomoses were carried out with the aorta partially clamped and the patient rewarmed.

Weaning from extracorporeal circulation is carried out following a staged plan. To avoid high doses of catecholamines, we favor the early use of some form of mechanical circulation support. All patients or their relatives, their cardiologist, or family doctor received questionaires regularly (every 6 months) or were contacted by telephone. The follow-up was 97.9% complete. The following variables were entered into a proportional hazards model (Cox) to elaborate on the factors that determine the postoperative course: age, gender, quality of the coronary arteries, myocardial viability, urgency, complete or incomplete revascularization, redo, number of bypass grafts, preoperative NYHA class, and ischemic time. To obtain dichotomous variables, good and fair coronary status were included together as one category (ie, viable and partially scarred myocardium) and preoperative NYHA classes I through III.

	Results

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The preoperative clinical profile of the patients is depicted in Table 1. Over the years of the study, the percentage of patients suffering from angina preoperatively decreased from 94% in 1988 to 34% in 1999. According to the definitions of the Canadian Cardiovascular Society, 253 patients were in class I, 202 in class II, 64 in class III, and 35 in class IV. According to the classification of the NYHA, 11 were in class I, 188 in class II, 542 in class III, and 167 in class IV. All patients had suffered previous myocardial infarctions: 195 had suffered one, 417 suffered two, 202 suffered three, 82 suffered four, and 12 suffered five. Three hundred and seventeen patients had undergone interventional treatment: 163 were treated once, 91 twice, 34 three times, and 29 more than three times. The hemodynamic profile of the patients is presented in Table 2. The number of akinetic segments per patient was 2.2, and the number of hypokinetic areas was 1.9 per patient. During the study period, an increasing number of patients (n = 695) underwent preoperative positron emission tomography scans to elucidate myocardial viability, whereas the numbers of scintigraphic examination (n = 299) decreased significantly. In 840 patients (92.5%), the targeted myocardial areas were found viable or partially scarred; in 68 patients, the myocardial areas were transmurally scarred. The left ventricular enddiastolic pressure was measured preoperatively in only 617 patients.

The nonlethal complications included perioperative myocardial infarction in 34 patients (3.7%), transient neurologic deficit in 67 (7.4%), stroke in 15 (1.7%), deterioration of the renal insufficiency in 69 (7.6%) (22 needed transient, 5 permanent dialysis), pulmonary insufficiency (time on respirator > 24 hours) in 165 (18.2%), pneumonia in 37 (4.1%), and ileus in 45 (6.0%). Twenty-six of these patients had a laparotomy. Mean time on the ventilator in the intensive care unit was 8.8 hours in all patients (range, 2 to 768 hours): 4.6 hours in patients with an uneventful course and 115 hours in patients who died perioperatively. The mean left ventricular ejection fraction (LVEF) for the whole series measured echocardiographically increased from 23.5% (± 5.9%) preoperatively to 32.4% (± 7.2%) on postoperative day 5 (p > 0.001). Six months after the operation, the LVEF rose to 36.6% (± 7.2%), and 12 months after the operation, to 36.5% (± 7.4%). All postoperative measurements were statistically different from the preoperative findings. In patients with poor coronary vascular systems, the LVEF was determined with 23.3% (± 6.1%) preoperatively, 24.2% (± 5.8%) postoperatively, 24.2% (± 6.0%) after 6 months, and 23.8% (± 6.9%) after 12 months.

These differences were not statistically significant. During the follow-up period (mean, 65 months), 100 patients (11%) died. One hundred and ninety-five patients (20.5%) developed heart failure: 20 of them (2.2%) underwent VAD implantation because a suitable donor organ could not be identified in time, and 24 (2.6%) were transplanted or are on the waiting list. Two hundred and ninety-nine episodes of ventricular arrhythmias were documented in 238 patients. Two hundred and one of these patients (84.5%) were suffering from ventricular arrhythmias preoperatively. Fifty-six patients received a defibrillator during the follow-up time. Of the 790 surviving patients, 526 (67%) are currently in NYHA class I or II, 235 (29%) are in class III, and 29 (4%) are in class IV. The most significant predictors of survival in the proportional hazards model were a good or fair coronary status, viable myocardium in the targeted areas, complete revascularization, preoperative NYHA class I to III, and the number of bypass grafts (Table 3). All other factors (previous surgery, gender, age, ischemic time) did not prove statistically significant. On the basis of all adverse cardiac events, the picture is slightly different (Table 4). The most significant predictors of event-free survival were a good or fair coronary status, viable myocardium in the targeted areas, an elective operation, a complete revascularization, and the number of bypass grafts. All other factors did not prove statistically significant. Statistically significant differences between patients with a good or fair (combined in one group) and a poor coronary status were noted not only perioperatively but also during the follow-up time (p > 0.001) (Fig 1). The second most important factor was the viability of the myocardium. The postoperative course of patients with more than 50% viable tissue in the targeted areas proved to be significantly better than the course of patients with more than 50% nonviable myocardium. However, the number of those patients is small (68) (Fig 2). The patients in whom a complete revascularization was technically possible did significantly better than those who could only be revascularized incompletely. The urgency of an operation proved the last statistically significant factor. The course of patients who were operated electively was better than the course of patients who needed an urgent or an emergency procedure. Other factors (age, gender, number of bypass grafts, ischemic time) did not prove statistically different.

View larger version (25K): [in this window] [in a new window]   Fig 1. Freedom from adverse events. Variable: quality of the coronary arteries. Circles = good/fair (353 adverse events in 805 patients); squares = poor (100 adverse events in 103 patients).

View larger version (24K): [in this window] [in a new window]   Fig 2. Freedom from adverse events. Variable: myocardial viability. Circles = viable (398 adverse events in 840 patients); squares = poor (54 adverse events in 68 patients).

	Comment

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The diagnosis of dysfunctional but viable myocardium is fraught with a variety of problems. Usually in this group of patients, a mixture of different dysfunctional myocardial states coexists. Additionally, almost all patients have visible scarring of the left ventricular myocardium, although the scarred areas differ considerably in size. Furthermore, some patients have left ventricular hypertrophy due to hypertensive heart disease. These facts combined with the limited spatial resolution of scintigraphic pictures only allow for an approximate judgment of viability. Reversibility of the myocardial dysfunction is dependent on a multitude of factors: 1) the correct diagnosis of a reversible dysfunction caused by chronic reduction of myocardial perfusion [20]; 2) the surgical restoration of flow in the targeted areas [3, 4, 10, 11, 14]; 3) the severity of the subcellular changes [17–19]; and 4) the duration of the chronic malperfusion [25]. The last two factors may explain why some patients benefit very early after the restoration of flow, whereas in others, the ventricular function takes months or even years to improve. In another group of patients, no improvement is seen at all. Reasons for this finding might be an irreversible dysfunction caused by a severely altered myocardium in which the subcellular degeneration is so pronounced that no regeneration is possible even after the restoration of perfusion. Pagano and associates [20] and Di Carli and associates [14] found a linear correlation between dysfunctional segments with hibernating myocardium and the changes in ejection fraction postoperatively. Another reason for only transient restoration of perfusion might be the early occlusion of the bypass grafts. Usually it is assumed that all of the grafts are patent when ventricular functions are compared pre- and postoperatively. In our own series of patients, only 110 underwent coronary angiography 2 to 12 months postoperatively, for clinical reasons only. These patients had received 341 bypass grafts. Forty-six grafts (13.5%) were found to be occluded. Although this analysis is not representative, it highlights the problem. In a group of patients suffering from severe left ventricular dysfunction, usually the filling pressure is increased as well as the wall stiffness. In combination with a partially scarred myocardium, the resistance in small coronary arterioles is markedly elevated, leading to a poor run-off from the bypass grafts. Interestingly, Samady and associates [21] found no significant difference in the outcome of patients with and without improvement of the left ventricular function postoperatively. They conclude that even without improvement in global left ventricular function, effective revascularization protects against ischemic events. Veenhuyzen and associates [22] reached identical conclusions: revascularization is associated with an independent reduction in mortality. Furthermore, they explained the lack of benefit from defibrillator therapy in the CABG Patch trial in patients with this effect. Our data led us to a different conclusion: the increase in the postoperative LVEF is much larger in patients with graftable arteries than in patients with a poor coronary vasculature. This effect is related to the increase in coronary perfusion provided by the revascularization. The completeness of surgical revascularization is another important factor for an uneventful course in this group of patients coronary bypass grafts, which is dependent on a multitude of factors.

In our series, most of the patients had suffered multiple myocardial infarctions and displayed multiple hypo or akinetic myocardial areas. Collateral vessels were visible in more than half of the patients (54%). An earlier analysis showed no difference in the postoperative course of these patients. Lee and associates [23] described hibernating myocardial areas as an "unstable substrate" suffering from repetitive ischemias, generating ventricular arrhythmias (VA) and contractile dysfunction. Every prevented ischemic event is considered an advantage for the postoperative course. In our series, ventricular arrhythmias were noted postoperatively in only 15.5% in patients who were suffering from VA preoperatively. These findings suggest that the extensive myocardial fibrosis already present at the time of the operation is the cause of the VA, and are in agreement with the findings of other groups and the CABG Patch trial [22]. Kaul and associates [12] found an increase in perioperative mortality when more bypass grafts were constructed. In their series, the mean ischemic time was 88 minutes, which seems relatively long. One of the risk factors for early postoperative mortality was the absence of retrograde cardioplegia use. In most series, an average of three distal anastomoses was performed. The cross-clamp times range from 24 to 88 minutes. The shortest cross-clamp times were published by surgeons using intermittent aortic cross-clamping as a means of myocardial protection [3, 20]. More than a quarter of the distal anastomoses in our series could be performed without clamping the aorta due to poor antegrade or retrograde flow in the targeted coronary arteries. Intermittent aortic cross-clamping has long been established as a reliable and safe method, even in high-risk patients [24].

Most of the patients had a severely impaired cardiac output but had adapted well to this state. If an operation in this group of patients must be performed urgently, prolonged acute myocardial ischemia is the main cause. This results in almost all cases in an even lower cardiac output state, affecting all other organ systems. The prognosis in these cases is grave, because many of these patients suffer not only from cardiac problems, but also from multiple organ failure. This tendency is reflected in the much better prognosis of patients operated electively. Patients who were preoperatively in NYHA functional classes III or better made a better recovery than patients in NYHA class IV. This might reflect the observation that in hibernating myocardium, the baseline myocardial bloodflow is normal or only slightly diminished, whereas the coronary vasodilator reserve is impaired [25]. Although the degree of impairment is variable, it was shown to be more severe in stenotic regions with resting dysfunction. Hemodynamic variables alone provide information only on the preoperative status. We were not able to identify a single variable or a combination of hemodynamic variables as statistically significant predictors of death or adverse events after surgical revascularization.

The perioperative mortality and morbidity in this study are low. One of the reasons might be the myocardial protection, as discussed above. Another important factor is the liberal use of mechanical circulatory support. In our experience, higher doses of catecholamines produce many adverse effects not only on the heart itself but also on other organ systems. These problems can be circumvented, at least in part, by using IABP. The morbidity of this method is low and it is simple to use. In only 10 patients was IABP not sufficient to support the circulation, and in 5 of these patients, a left ventricular assist device was implanted; in the 5 remaining patients, a biventricular system was implanted in the operating room.

In a small number of patients (n = 3), it was only detected intraoperativly that the free wall of the left ventricle was very thin and the myocardium was largely replaced by scar tissue. In these patients, assist devices were implanted to prevent low cardiac output syndrome, and the patients were put on the waiting list for heart transplantation.

The percentage of patients suffering from angina decreased continously over the years, from 94% in 1988 to 34% in 1999. Surprisingly, the course of patients suffering from angina was not different from those who had never experienced angina. This is contradictory to earlier results, where patients suffering from angina did better than patients free from angina [7, 8]. We, along with others [20], were not able to detect statistically significant differences in patients undergoing redo operations or in female or diabetic patients [12]. These "classic" risk factors seem to have only limited influence on the outcome in this highly selected series of patients. The same holds true for age at the time of operation. These study patients in our center are on average more than 8 years younger than those patients without left ventricular dysfunction. ([9])

	Acknowledgments

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We gratefully acknowledge the help of Dr Edward Murray in the preparation and translation of the manuscript.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

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