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Ann Thorac Surg 1999;67:404-410
© 1999 The Society of Thoracic Surgeons
a Cardiothoracic Unit, Freeman Hospital, Newcastle upon Tyne, United Kingdom
b Department of Medical Statistics, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
Accepted for publication June 27, 1998.
Address reprint requests to Dr Bourke, University Department of Cardiology, Freeman Hospital, Freeman Rd, Newcastle upon Tyne, NE7 7DN, United Kingdom
| Abstract |
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Methods. Thirteen variables suggested by other researchers as predictive of outcome were analyzed. At the time of study, ER was the only therapy available for drug refractory VT.
Results. Only emergency ER, wall motion score less than 3 and Killip classification were significantly related to death from cardiac failure. The lack of correlation between emergency ER and variables of ER timing, VT less than 24 hours of ER or VT type implies that the need for emergency ER is also related to ventricular dysfunction. Multivariate analysis identified a group at particularly low risk of death with a specificity of 95%.
Conclusions. Patients at low risk of death after ER can be identified prospectively. In the implantable cardioverter defibrillator era, elective ER is best reserved for such patients. Emergency ER may still be justified in younger patients without comorbidity who will die of VT without it.
| Introduction |
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The aim of this analysis was to determine whether patients who died of low output cardiac failure within 30 days of map-guided endocardial resection for postinfarction ventricular tachycardia could have been differentiated from those who did not on the basis of preoperative variables already suggested as predictive of outcome by other units.
| Material and methods |
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The outcome to be predicted, death from low output cardiac failure, was defined as death on the intensive care unit within 30 days after operation despite extensive pharmacologic and intraaortic balloon pump support. All such deaths occurred in the context of hypotension, oliguria, and progressive organ failure with the patient never having been weaned from ventilatory support. For the purpose of this analysis, death from any other cause was analyzed as if the patient had survived.
Univariate parameters
Elective versus emergency operation
Previous studies [4, 5], including a pilot study from this unit, showed "emergency operation" to be the single parameter most predictive of death within 30 days after operation. Emergency operation was defined as any operation undertaken that had not been planned more than 24 hours previously. This was synonymous with operation undertaken in the context of frequent or incessant arrhythmias and implied that without operation the patients anticipated mortality approached 100%. Elective procedure was any nonemergency operation.
Ventricular arrhythmias in the 24-hour period before operation
The occurrence of major episodes of arrhythmia in the period immediately before operation might be a reason to delay the operation [4, 8]. However, delay in this context might also allow time for further arrhythmias with cumulative deterioration in ventricular function from resuscitation [11].
Timing of operation
Proximity of operation to infarction has been identified by some investigators as adversely affecting outcome [4, 5, 10]. This analysis, therefore, included both the time from acute infarction to the first major arrhythmia and from infarction to operation both measured in days.
Type of ventricular arrhythmia
Patients were grouped into those who had only ever experienced sustained monomorphic ventricular tachycardia and those whose episodes of monomorphic tachycardia sometimes degenerated to ventricular fibrillation.
Age
Several studies have suggested that patients more than 65 years are not suitable for antiarrhythmic operation [1214]. In this analysis, the effect of age on survival was assessed in decade measurements.
Total bypass time
Although not a preoperative variable, the total bypass time in minutes was used as an index of the complexity and duration of the operation [13, 15].
Measures of left ventricular dysfunction
Previously published reports disagree as to whether and which parameters of left ventricular function are useful in outcome prediction and in the selection of patients for operation [4, 5, 8, 16, 17].
Therefore, the relationship between seven preoperative measures of left ventricular function were assessed. The variables studied were (1) left ventricular ejection fraction [4, 5, 8, 16, 17]; (2) left ventricular "excess" ejection fraction [5, 18]; (3) wall motion score [6, 17]; (4) left ventricular end-diastolic pressure [4]; (5) presence or absence of a left ventricular aneurysm [4, 5, 19]; (6) Killip classification of the degree of clinical heart failure present immediately before operation [16, 20]; and (7) extent of coronary artery disease [4, 8, 18].
Left ventricular ejection fraction was calculated from the right anterior oblique view of the left ventricular cine-angiogram by planimetry and expressed as a percentage. Left ventricular excess ejection fraction, devised to reflect ventricular function in the noninfarcted segments, was calculated by the method originally described [21]. Left ventricular end-diastolic pressure, in mm Hg, was taken as the mean peak A-wave pressure recorded at the time of the left ventricular angiogram [15].
Wall motion scores could be calculated for patients who had biplane left ventricular cine-angiography performed. The ventricle was divided into nine segments and the amplitude of systolic motion of each segment scored by a method previously described by two experienced observers blinded to the patients details [6]. A score of 0 indicated normal systolic motion and a score of 6, aneurysmal paradoxical systolic motion. For the purpose of this analysis, 30-day outcome was compared between patients who had three or more or less than three segments with normal systolic motion [6, 13].
The presence or absence of a left ventricular aneurysm before operation was also studied separately from other variables. Left ventricular aneurysmectomy was performed for circumscribed areas of left ventricular scar with dyskinetic systolic motion, identified by ventriculography and confirmed at operation.
Clinical signs of heart failure were graded according to the Killip classification in each patient from the last examination before operation [20], for example, class I: no evidence of heart failure; class II: increased jugular venous pressure or presence of a third heart sound; class III: clinical or radiographic evidence of pulmonary edema; and class IV: cardiogenic shock.
The extent of coronary artery disease was assessed from the preoperative arteriograms. Patients were classified as having single-, double-, or triple-vessel disease on the basis of having a 75% or greater stenosis in a major epicardial artery [22].
Statistical analyses
Each variable was entered into a logistic regression model in turn to determine whether it was potentially predictive of death from low-output cardiac failure within 30 days of operation. Those that approached statistical significance (p < 0.2) were considered in combination, to determine the optimum model in terms of goodness of fit. This was judged in terms of model deviance. Missing values meant that some univariate regression models were based on different numbers of observations. This was a greater problem when variables were examined in combination. It meant that objective statistical criteria could not be used strictly to determine the final model. Results are presented as odds ratios with corresponding 95% confidence intervals and models were evaluated in terms of sensitivity (percentage of patients who died who were predicted to be at high risk of death), specificity (percentage of patients who survived who were predicted to be at low risk of death), positive predictive values (percentage of patients who were predicted to be of high risk of death who died), and negative predictive value (percentage of patients who were predicted to be at low risk of death who survived).
| Results |
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Arrhythmias within 24 hours of operation
Thirty-six patients experienced a major episode of arrhythmia in the 24 hours before operation. Sixteen patients had a single arrhythmia episode, 5 had two, 6 had three, and 9 had five or more episodes. Most episodes required cardioversion for control. In 3 additional patients ventricular tachycardia was well tolerated but incessant. Univariate analysis showed no difference between those who did and did not experience a major arrhythmic event within 24 hours of operation in the incidence of death from cardiac failure postoperatively (univariate odds ratio = 1.78; 95% CI = 0.67 to 4.74).
Timing of operation
The median time from infarction to arrhythmia onset was 4 weeks. No difference was identified in this parameter between those who died and those who survived the early postoperative period (univariate odds ratio = 0.9; CI = 0.69 to 1.16).
Fourteen patients underwent operation within 1 month, 32 within 2 months, and 37 within 3 months of infarction. No difference in proximity of operation to infarction was identified between those who died and those who survived the early postoperative period (univariate odds ratio based on log data = 1.0; 95% CI = 0.67 to 1.20).
Arrhythmia type
In 50 patients the only arrhythmia documented was sustained monomorphic ventricular tachycardia. In the remaining 50, some episodes of ventricular tachycardia degenerated into ventricular fibrillation. Degeneration to ventricular fibrillation did not distinguish patients who died in the early postoperative period from those who survived (univariate odds ratio = 1.13; 95% CI = 0.43 to 11.17).
Age
During the time of this data collection no patient was rejected for operation on grounds of age. The age range of patients included was 13 to 75 years and 16 patients were more than 65 years. Despite this, age was not predictive of early postoperative outcome (univariate odds ratio = 1.19; 95% CI = 0.69 to 2.05, odds expressed per decade of age increase).
Bypass time
Median bypass time was 157 minutes (range, 61 to 449 minutes). Total bypass time was not predictive of death from cardiac failure (univariate odds ratio from log data = 2.5; 95% CI = 0.56 to 1 1.17).
Assessments of left ventricular function preoperatively
The predictive values of each of the seven measures of left ventricular function assessed for low output cardiac failure within 30 days of operation are summarized in Table 2.
Only the patients Killip class (odds ratio: Killip class II, 3.24, 95% CI = 0.98 to 10.73; Killip class III/IV, 6.43, 95% CI = 1.47 to 28.05) and wall motion score (univariate odds ratio 3.45; 95% CI = 0.94 to 12.73) before operation were significantly related to postoperative outcome.
None of the other five variables (ejection fraction, excess ejection fraction, left ventricular end-diastolic pressure, extent of coronary artery disease presence, or absence of an aneurysm) were significantly related to death from cardiac failure.
Killip class or wall motion score as a derived composite variable
Both Killip class and wall motion score appeared predictive of death from cardiac failure within 30 days of operation. However, one of these variables was unavailable in 24 patients and 6 of these died after operation. This constituted too large a proportion of the data set to ignore in comparing the relative merits of Killip class and wall motion score in predicting early death; therefore, a composite variable was created. This new variable divided patients into (1) those whose wall motion score was less than three or who were in Killip class III or IV and (2) those whose wall motion score was three or more and who were in Killip class I or II. The composite variable was compared in terms of model fit with the Killip classification and the wall motion score variables. The predictive value of the new variable (odds ratio = 4.19; 95% CI = 1.45 to 12.09) was comparable to that of wall motion score in terms of model fit and slightly better than Killip class alone.
Outcome prediction and patient selection for operation
The two strongest predictors of early postoperative outcome, based on this retrospective analysis, are the variable combining wall motion score/Killip class and the variable of emergency/elective operation. Tables 3 and 4 summarize the accuracy of predicting death from low output cardiac failure in the early postoperative period based on whether a patient is at increased risk based on both or neither of these two variables. The model that best fits the data is that containing both the combined wall motion score/Killip class variable and the emergency/elective operation variable. This model could be used to predict the high risk of death in different ways, the two most obvious being: (1) predict a patient to be at high risk of death if he or she has an adverse combined wall motion score/Killip class or is undergoing emergency operation, (2) predicts a patient to be at high risk of death if he or she has an adverse combined wall motion/Killip class and is undergoing emergency operation. In case 1, patients must fulfill either of the criteria to be considered high risk and in our series this accounted for 37% of patients. In case 2, patients must fulfill both criteria to be considered high risk and in our series this accounted for 10% of patients. As shown in Table 4, the negative predictive values of both cases are comparable but the population of patients deemed at high and low risk in the two examples is different.
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Optimal selection of patients for antiarrhythmic operation
The object in selecting and rejecting patients for any particular therapy is to maximize the benefits and encourage referral of those most suitable, while recommending alternatives to those likely to be disadvantaged by it. This can be justified both on medical and health economic grounds. The range of treatments for patients with postinfarction ventricular tachycardia include antiarrhythmic drugs, the implantable cardioverter defibrillator, catheter or surgical ablation, and cardiac transplantation. Not all patients are suitable for each treatment and therapies are not always successful. The task for the clinician is to individualize therapy for the patient in the light of detailed assessments, striking the best balance between the risk posed by arrhythmia recurrences and the riskbenefit equation and cost of the therapy being recommended. The most common cause of death within 30 days of operation was low output cardiac failure [13]. It would be anticipated that this mode of death would relate to the degree of left ventricular dysfunction present preoperatively [4]. The fact that only two of seven measures of left ventricular function studied related to outcome may be attributable to the crudity of the measures themselves, to the inability of any single static measurement to reflect the variability critically determining survival in patients with precarious ventricular function, or to the fact that preoperative measures are swamped by intraoperative influences. The predictive value for early outcome of wall motion score and functional cardiac status, as measured by either New York Heart Association or Killip class, are confirmed by other researchers [46, 8, 17, 19, 20]. However, the lack of association between outcome and ejection fraction, excess ejection fraction, and age are at odds with earlier published studies from several groups [5, 17, 18]. Whatever the reason for their failure to predict outcome in this and other studies, these results suggest that it is inappropriate to select patients for operation on the basis of left ventricular ejection fraction, excess ejection fraction, end-diastolic pressure, extent of coronary artery disease, or aneurysmal status. It seems equally inappropriate to use age as a reason to preclude patients from operation [1214]. Although age may code for comorbidity, there is no evidence from this study that age alone is an adverse prognosticator.
Emergency versus elective operation
The finding that emergency operation carries an adverse prognosis can be interpreted in two ways. The first would suggest that operation in this context should be avoided and treatment focused on stabilizing the patient without operation. Postponing operation until the patient was stable would allow the operation to be undertaken later at the lower elective risk. The alternative interpretation is that the need for emergency operation identifies a patient with a particularly poor prognosis of which the frequency of arrhythmias is only one manifestation. If this were so, then either it would not be possible to defer operation without a substantial mortality or, even if deferred to a later date, it would carry the higher emergency mortality rate.
The fact that neither the time from infarction to operation nor the occurrence of arrhythmias in the immediate preoperative period related to outcome suggests that emergency operation is not a procedure performed inappropriately early, but rather that frequent arrhythmias are a manifestation of more damaged ventricles. Delaying an emergency operation would be unlikely, therefore, to improve the outcome of endocardial resection at a later date and would result in a high initial arrhythmia-related mortality because the majority of patients could not be stabilized. Patients in this category who survived this conservative phase would be self-selected survivors who might number less than those from the initial group who would have survived emergency operation. On the basis of the experience in this hospital, there is no suggestion that patients requiring emergency operation become more suitable for antiarrhythmic operation subsequently, rather that they are only suitable for cardiac transplantation.
Can low-risk patients be identified for operation?
In the clinical context the ability to predict patients who will die of low output cardiac failure within 30 days of operation is less important than identifying those who are at minimal risk of this complication. With the currently available choice of antiarrhythmic therapies, patients in the higher risk categories referred for elective operation in this study would now be recommended either for cardioverter-defibrillator therapy or for cardiac transplantation. The management of patients in the intermediate risk category would vary depending on the resources available, the hemodynamic implication of the arrhythmias, the presence of additional surgical indications, and the patients treatment preference.
The results of this analysis showed that elective operation was performed in this series with a 13% (8 of 63 patients) 30-day mortality rate in patients who had at least three left ventricular segments contracting normally and who were in Killip class I or II. This compares with the 1% to 5% figure quoted from surgical series of patients treated in the defibrillator era [13, 23, 24].
Although death from cardiac failure is the most common cause of death in surgical series and the only outcome studied in this analysis, it is not the only concern. At present, in recommending elective operation to patients, it is likely that comorbidity would increase selection bias in favor of fitter patients. Furthermore, arrhythmia characteristics, such as accessibility of substrate and number of arrhythmia generators, would also need to be considered to determine the likelihood of arrhythmia cure [4, 5, 8, 13, 25].
The management of patients who in the past have been offered emergency operation remains a difficult clinical problem. It is clear that they are at particular risk from postoperative death primarily attributable to the severity of left ventricular dysfunction. To what extent antiarrhythmic drug therapies administered in the hours before operation reduce their survival chances after operation is still unknown [4]. Their best treatment is cardiac transplantation when it is available. However, in the absence of such an option, an antiarrhythmic procedure may still offer survival to a group whose mortality approaches 100% without it. The extent to which such patients should be supported in the hope of a suitable donor becoming available remains an issue to be determined on a unit by unit basis [26].
In conclusion, this analysis confirms the difficulty in predicting death from low output cardiac failure after antiarrhythmic operation from preoperative variables for an individual patient. Left ventricular function as expressed by wall motion score, Killip class, and emergency or elective procedure is the best preoperative indicator of early postoperative outcome. The best predictive model identified has a high negative predictive value and this is unlikely to be improved by the inclusion of other variables not considered in this analysis. Although far from ideal, a consensus can be identified from this and other similar analyses that allows a group of low-risk surgical patients to be identified. At the present time, this "ideal" group at least should be considered for antiarrhythmic operation.
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