Anesth Analg 2002;95:517-523
© 2002 International Anesthesia Research Society
CARDIOVASCULAR ANESTHESIA
Is There a Long-Term Predictive Value of Intraoperative Low-Dose Dobutamine Echocardiography in Patients Who Have Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass?
Frank W. Dupont, MD*,
Roberto M. Lang, MD FACC
,
Melinda L. Drum, PhD
, and
Solomon Aronson, MD FACC, FACCP*
Departments of *Anesthesia and Critical Care, Cardiology, and Health Studies, University of Chicago, Chicago, Illinois
Address correspondence and reprint requests to Solomon Aronson, MD, University of Chicago, Department of Anesthesia and Critical Care, 5841 S. Maryland Ave., Box 4028, Chicago, IL 60637. Address e-mail to aronson{at}airway.uchicago.edu
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Abstract
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In patients with coronary artery disease, chronic regional left ventricular systolic dysfunction at rest may be caused by hibernating or by infarcted myocardium. Intraoperative low-dose dobutamine (LDD) echocardiography reliably predicts the immediate recovery of regional myocardial function after coronary artery bypass graft (CABG) surgery. We sought to determine whether intraoperative LDD echocardiography would also predict recovery of regional function after 1 yr. Twenty-five patients with coronary artery disease who underwent CABG surgery with intraoperative LDD echocardiography were evaluated 1 yr later with a follow-up transthoracic echocardiogram. The covariates of left ventricular ejection fraction, old myocardial infarction, and diabetes mellitus were considered in an analysis of regional wall motion (RWM). A 16-segment model and a 1–5-point scoring system were used to evaluate 350 myocardial segments. Multiple logistic regression analysis was performed to determine whether response to intraoperative LDD echocardiography (5 µg · kg-1 · min-1) predicted changes in regional function at 1 yr. A segment was defined as stunned if the RWM score obtained during LDD infusion deteriorated after cardiopulmonary bypass but recovered in the 1-yr follow-up echocardiogram. A response to intraoperative LDD predicted changes in regional function at 1 yr. The overall odds of improvement in regional function were 2.22 times greater (95% confidence interval = 1.29, 3.82; P = 0.0039) with a positive response to intraoperative LDD. The positive predictive value of intraoperative LDD echocardiography for improvement in myocardial function was 0.81 and the negative predictive value was 0.34. The predictive values did not vary with the examined covariates. Of segments with unexpected deterioration of RWM immediately after cardiopulmonary bypass, 87% recovered at the time of the 1-yr follow-up echocardiogram. Contractile reserve demonstrated by intraoperative LDD echocardiography predicts regional function at 1 yr; however, the test cannot predict which segment will not recover. Most of unexpected regional ventricular systolic dysfunction immediately after CABG surgery can be attributed to myocardial stunning.
IMPLICATIONS: In patients undergoing coronary artery bypass graft surgery, intraoperative low-dose dobutamine echocardiography has only limited value for the prediction of regional myocardial function at 1 yr. Small-dose dobutamine echocardiography predicts regional myocardial function at 1 yr when baseline regional wall motion abnormalities improve with dobutamine; however, the test cannot be used to predict which segment will not recover at 1 yr.
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Introduction
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Viable myocardium is defined by the presence of living myocytes, whereas nonviable myocardium exists in infarcted (necrosed) tissue (1). Viable myocardium may be normally contracting or dysfunctional in the state of acute ischemia, stunning, or hibernation. In acute myocardial ischemia, decrease in regional myocardial blood flow and contractility is proportional (acute perfusion-contraction mismatch) (2). In myocardial stunning, a fully reversible dysfunction persists after reperfusion despite restoration of normal or near-normal coronary blood flow (perfusion-contraction mismatch) (3). In myocardial hibernation, left ventricular dysfunction attributed to chronic coronary artery disease (CAD) is reversible (4). It is characterized by normal or slightly reduced myocardial blood flow and limited coronary flow reserve (5–7). There is residual contractile reserve with adrenergic stimulation, and regional and global ventricular function can improve after revascularization (8,9).
In patients with CAD, chronic regional left ventricular systolic dysfunction at rest may be caused by hibernating or by infarcted myocardium. Intraoperatively, it is critical to distinguish dysfunctional but viable myocardial regions from dysfunctional and nonviable regions because therapeutic strategies depend on differentiation between reversible and nonreversible dysfunction. Likewise, an evaluation of the adequacy of revascularization during surgery depends on the ability to predict changes in the flow-function dynamic immediately after surgery (7). Improvement in left ventricular systolic function after coronary artery bypass graft (CABG) surgery, however, is not easily predicted before revascularization by assessment of baseline function with angiography or echocardiography (10–12). Recovery of function after coronary revascularization depends on many factors including, but not limited to, the severity of preoperative global left ventricular dysfunction, myocardial protection techniques, and the adequacy of revascularization (13). Intraoperative low-dose dobutamine (LDD) echocardiography reliably predicts immediate recovery of regional function after CABG surgery (14). The predictive value of intraoperative LDD echocardiography for recovery of regional contractile function immediately after CABG surgery is independent of left ventricular ejection fraction, old myocardial infarction, diabetes mellitus, and preoperative ß-adrenergic blocker use (14). We previously concluded that changes observed in regional function after the administration of LDD represent a "gold standard" to detect functional changes expected after successful revascularization.
In this study, we tested the hypothesis that intraoperative LDD echocardiography would predict regional myocardial recovery 1 yr after patients had CABG surgery with cardiopulmonary bypass (CPB).
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Methods
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After approval from our institutional review board, 40 patients who had elective CABG surgery with intraoperative LDD echocardiography (14) were contacted for a transthoracic echocardiogram 1 yr after surgery. Informed consent was obtained from all subjects. Preoperative history and physical examination, medications, and results of diagnostic tests were recorded, including data from coronary angiography, preoperative echocardiography, electrocardiogram, and thallium perfusion scans. Criteria for an old myocardial infarction were Q-waves on the electrocardiogram, an irreversible defect on a thallium perfusion scan, or both.
LDD Echocardiography Protocol
The protocol for LDD echocardiography has been described in detail elsewhere, and is diagrammed in Figure 1 (14). In summary, regional wall motion (RWM) was evaluated by using transesophageal echocardiography at four stages: after the induction of anesthesia (baseline), after the infusion of 5 µg · kg-1 · min-1 dobutamine before surgical incision (LDD), after separation from CPB (early), and after the administration of protamine (late). Recorded images were digitally stored in loop formation with electrocardiogram R-wave triggering to capture a representative cardiac cycle in each view. The selected cycle was displayed in a continuous loop in quad-screen format to evaluate regional shortening fraction and systolic wall thickening. Two observers independently compared all images off-line simultaneously at each stage (baseline, LDD, after CPB, and after protamine) in each view. Regional wall motion was assessed by using a 5-point scoring system: 0 = unable to image, 1 = normal, 2 = mild hypokinesia, 3 = severe hypokinesia, 4 = akinesia, 5 = dyskinesia. An RWM score was assigned to each segment at each stage by each observer. Redundant segments in different image planes were not scored twice, and the segment in the mid-transgastric short-axis view was recorded. If there was disagreement between observers, a third score was sought from another observer who was blinded to the scores of the first two. The final score was derived by consensus of all three observers when there was disagreement. Contractile reserve was considered present if an abnormal RWM improved with LDD infusion. Abnormal segments at rest that improved by 
1 score with dobutamine infusion were considered hibernating segments unless there was evidence to the contrary, such as a history of acute myocardial ischemia-reperfusion. If an abnormal segment did not improve during the dobutamine infusion, it was considered infarcted, and no improvement in regional contraction patterns was expected with surgical revascularization. An abnormal segment that worsened during LDD infusion was considered ischemic. A segment was regarded as stunned if the RWM score obtained during LDD infusion deteriorated after early separation from CPB or protamine administration but recovered in the 1-yr follow-up echocardiogram. The response of abnormal segments to LDD did not influence the surgical decision to revascularize stenotic coronary arteries. Surgical revascularization was considered successful if RWM after CABG surgery was similar to the improvement in RWM noted during dobutamine infusion.
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Figure 1. Diagram of the protocol for low-dose dobutamine (LDD) echocardiography. CPB = cardiopulmonary bypass, early = after separation from CPB, late = after the administration of protamine.
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Transthoracic Echocardiography
The transthoracic echocardiographic examination (Hewlett Packard 5500, Andover, MA) was performed by an experienced ultrasonographer with the patient in the left semisupine position. Images were acquired in the apical four-chamber, apical two-chamber, parasternal long-axis, and short-axis view for analysis of multiple segments of the left ventricle. These images were compared with the intraoperative images obtained at the time of the transesophageal examination and corresponded to the midesophageal four-chamber, midesophageal two-chamber, midesophageal long-axis, and transgastric midpapillary short-axis view. Internal frames of reference were used to compare echocardiographic images. Recorded images were stored digitally as cineloops. The selected cycle was displayed in a continuous cineloop to evaluate changes in RWM. An independent observer, unaware of the scores obtained during the intraoperative LDD echocardiography examination, assessed RWM by using the previously described scoring system. Redundant segments in different image planes were not scored twice, and the score of the segment in the parasternal short-axis view was recorded.
The RWM scores were analyzed by using the generalized estimating equation (GEE) extension of multiple logistic regression analysis for correlated data (15) to determine whether intraoperative LDD echocardiography predicted changes in regional myocardial function from baseline (before CABG surgery) at 1 yr. Both positive and negative predictive values of LDD echocardiography for changes in regional myocardial function 1 yr after coronary revascularization were computed. Odds ratios for improvement of RWM abnormalities at 1 yr were determined for response to LDD. The influence of the covariates (previous myocardial infarction, preoperative left ventricular ejection fraction, and diabetes mellitus) was also analyzed. The logistic regression analyses were performed by using the GENMOD procedure in SAS statistical analysis software (16). This procedure for logistic regression and other generalized linear models includes the option of GEE estimation for correlated data (15). The Fisher’s exact test and the 
2 test of association were used to compare patients with and without follow-up echocardiogram.
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Results
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Of 40 patients eligible for follow-up transthoracic echocardiogram, 25 returned for evaluation at 1 yr. The other 15 patients were contacted by telephone but decided not to participate. The average age of the patients enrolled was 63 ± 10 yr (range, 39–80 yr). There were 18 men and 7 women: 11 had a left ventricular ejection fraction >0.45, 9 had an old Q-wave myocardial infarction, 13 had diabetes mellitus, and 13 were taking ß-adrenergic blockers at the time of surgery (Table 1). No significant differences were detected among patients who returned for follow-up and those who did not in age, sex, preoperative left ventricular ejection fraction, old myocardial infarction, diabetes mellitus, preoperative use of ß-adrenergic blocker, and abnormal scores for baseline RWM (Table 1).
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Table 1. Table 1. Comparison of Patient Baseline Characteristics and Intraoperative Regional Wall Motion Scores Between Patients Who Did and Did Not Return for an Echocardiogram at 1 Year
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Because the midesophageal long-axis view was not acquired intraoperatively in all patients during the protocol, the segments unique to this view were eliminated from the analysis. Fourteen segments in each patient were scored for a total of 350 segments in 25 patients. At baseline (after the induction of anesthesia but before surgical incision), 184 were abnormal compared with 166 that were normal (Figs. 2 and 3). Because of inadequate image quality, 29 segments were assigned a score of 0 at one of the stages in the protocol. Overall, intraoperative LDD echocardiography had a positive predictive value of 0.81 and a negative predictive value of 0.34 at 1-yr follow-up. Given improvement with intraoperative LDD, there was approximately a 2.2-fold increase in the odds of improvement from baseline RWM abnormalities in the 1-yr follow-up transthoracic echocardiogram (odds ratio = 2.22; 95% confidence interval = 1.29, 3.82; P = 0.0039). Predictive values of intraoperative LDD echocardiography were independent of preoperative left ventricular ejection fraction, old myocardial infarction, or diabetic status.
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Figure 2. Changes in regional contractile function from baseline of abnormal segments during the infusion of low-dose dobutamine (LDD). Evaluation was made at these time points: baseline, after the induction of anesthesia; LDD; early, after separation from cardiopulmonary bypass; late, after the administration of protamine; 1 yr, at 1-yr follow-up transthoracic echocardiogram. Symbols: + = improved, = = no change, - = worse. The numbers refer to the number of myocardial segments.
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Figure 3. Changes in regional contractile function from baseline of normal segments during the infusion of low-dose dobutamine. Evaluation was made at these time points: baseline, after the induction of anesthesia; low-dose dobutamine (LDD); early, after separation from cardiopulmonary bypass; late, after the administration of protamine; 1 yr, at 1-yr follow-up transthoracic echocardiogram. Symbols: + = improved, = = no change, - = worse. The numbers refer to the number of myocardial segments.
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Of 350 segments, 30 had a worse RWM score after CPB than at the time of the LDD infusion. At the 1-yr follow-up echocardiogram, 26 of 30 segments (87%) recovered (9 improved and 17 were unchanged from their RWM score during the LDD infusion) and therefore were considered stunned segments. Four segments had a worse RWM score in the follow-up echocardiogram than during LDD infusion.
During the LDD infusion, only one segment had an ischemic response. This segment deteriorated one grade from its baseline score (mild hypokinesis to severe hypokinesis); it was akinetic early after CPB, severely hypokinetic after protamine administration, and mildly hypokinetic on the 1-yr follow-up echocardiogram.
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Discussion
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Three main conclusions can be drawn from our study: 1) intraoperative LDD echocardiography predicts regional myocardial function at one year when baseline RWM abnormalities improve with LDD, 2) if baseline RWM abnormalities fail to respond to intraoperative LDD before revascularization, then changes in regional function after one year cannot be predicted, and 3) most of unexpected regional ventricular systolic dysfunction immediately after CABG surgery can be attributed to myocardial stunning.
Predictive Value of Intraoperative LDD Echocardiography
Chronic regional left ventricular systolic dysfunction at rest in patients with CAD may be caused by hibernating or by infarcted myocardium. Preoperatively, it is important to distinguish hibernating myocardial regions from necrotic areas before CABG surgery because revascularization of hibernating myocardium decreases perioperative and long-term morbidity and mortality, and improves left ventricular systolic function (17–19).
Low-dose dobutamine echocardiography, a widely used method to differentiate between reversible and irreversible regional dysfunction in the ambulatory setting, predicts regional and global recovery of function after revascularization treatment in patients with chronic ischemic left ventricular dysfunction (20). The diverging contractile response between hibernating and infarcted myocardium makes possible the distinction between reversible and irreversible tissue injury. Low-dose dobutamine elicits an improved contractile response from hibernating but not from infarcted myocardium. Overall, LDD echocardiography in an ambulatory setting can predict the reversibility of regional myocardial dysfunction with a sensitivity of 84% and a specificity of 81% (7). When augmentation of function with a low dose is followed by progressive systolic dysfunction at higher doses (biphasic response), the accuracy of predicting changes in regional function after revascularization is even greater (21). A comparison of LDD echocardiography with positron emission tomography and radionuclide techniques has established LDD echocardiography as an accurate test to predict the recovery of myocardial function after revascularization (22). Low-dose dobutamine testing with transesophageal echocardiography has a sensitivity of 96% and a specificity of 88% and compares favorably with the same sensitivity but a specificity of 69% in positron emission tomography (13).
The positive predictive value of intraoperative LDD echocardiography for improvement in regional myocardial function at 1 year was 0.83, independent of left ventricular ejection fraction, a history of myocardial infarction, or diabetic status. The negative predictive value of intraoperative LDD echocardiography at one year was much lower. Therefore, LDD echocardiography can be used to predict regional myocardial function at 1 year when baseline RWM abnormalities improve with dobutamine; however, the test cannot be used to predict which segment will not recover at 1 year if no improvement is noted at a dose of 5 µg · kg-1 · min-1.
Several explanations are possible for the low negative predictive value of the test. The dose of 5 µg · kg-1 · min-1 may not be sufficient to cause the expected response, particularly if the concomitantly administered anesthetics cause a negative inotropic effect. At the time of separation from CPB, anesthetics may contribute again to a negative inotropic effect that was absent at the one-year follow-up echocardiogram. Accordingly, the long-term negative predictive value of intraoperative LDD echocardiography would be reduced. Second, complete coronary revascularization of hibernating myocardium may provide a greater long-term improvement in contractile function, which is not evident during intraoperative infusion of LDD or in the immediate reperfusion period. Third, loading conditions at acquisition time, particularly after separation from CPB, are dynamic and may confound the analysis of RWM (23). Increasing the upper limit of the LDD infusion as well as using new modalities for the assessment of regional left ventricular function, such as strain Doppler echocardiography may prove to be a more accurate predictor of functional recovery. The latter technique may be especially useful because it seems to be a load independent index of regional systolic function (24).
Regional Myocardial Dysfunction After CPB
Myocardial stunning describes prolonged but reversible contractile dysfunction after reperfusion after a state of low coronary blood flow (3). A deterioration of RWM from baseline with preserved myocardial perfusion is described in stunned segments as a "perfusion-contraction mismatch." We defined a segment as stunned if the RWM score predicted from LDD infusion was worse after CPB but recovered at the time of the one-year follow-up echocardiogram (14). The data from our study suggest that most of the unexpected regional myocardial dysfunction immediately after CABG surgery can be attributed to stunning because 87% of these segments recovered at the one-year follow-up echocardiogram.
Limitations
We acknowledge several limitations of our study. Because only 25 of the eligible 40 patients who had CABG surgery could be recruited for the follow-up echocardiogram, the follow-up cohort may not be representative of the entire study population. Nevertheless, baseline characteristics and intraoperative RWM scores of the returning 25 patients did not differ from those of the entire population. A second confounding factor in the interpretation of RWM abnormalities was the inconsistent report of ß-adrenergic blocker use in patients who returned for the transthoracic echocardiogram. Chart documentation was not reliable in the follow-up group because continuation and discontinuation of ß-adrenergic blocker was not always documented. Finally, evaluation of RWM excluded the basal anteroseptal and posterior segments because these segments were not consistently captured in all patients. The inclusion of these regions into the model may have affected the long-term predictive value of LDD echocardiography.
In patients undergoing CABG surgery with CPB, intraoperative LDD echocardiography has limited long-term predictive value. The response of myocardial segments to intraoperative LDD predicts regional function at one year; however, the test cannot be used to predict which segment will not recover at one year. Most unexpected regional myocardial dysfunction immediately after CABG surgery can be attributed to stunning. Assessment of regional myocardial function by strain Doppler analysis deserves clinical evaluation to determine whether it improves the diagnostic accuracy of intraoperative LDD echocardiography.
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Footnotes
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Presented in part at the annual meeting of the American Society of Anesthesiologists, San Francisco, CA, 2000.
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Accepted for publication May 3, 2002.
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Abstract
Introduction
