Postextrasystolic Potentiation and Dobutamine Echocardiography in Predicting Recovery of Myocardial Function After Coronary Bypass Revascularization
Background Identification of viable but hibernating myocardium remains a relevant issue in the current era of myocardial revascularization. Echocardiography can be helpful in detecting reversible contractile dysfunction and optimizing the selection of patients for coronary bypass surgery.
Methods and Results Eighty-four consecutive candidates for bypass surgery with chronic multivessel coronary artery disease were screened, and 60 were included in this prospective study. Preoperative evaluation of a reversible contractile dysfunction in asynergic myocardial regions was performed by dobutamine infusion at 5 (low dose) and 10 (intermediate dose) μg·kg−1·min−1 with each stage lasting at least 5 minutes; postextrasystolic potentiation (PESP), with a coupling interval ranging from 500 to 300 ms with a progressive 10-ms decrease; or a combination of both dobutamine infusion and PESP. Sensitivity (92% versus 86%) and predictive accuracy (89% versus 84%) were higher with PESP than dobutamine (P=.009 and P=.001, respectively), but the combination did not improve sensitivity or accuracy. Dobutamine induced ischemic dysfunction in 15% of patients at the intermediate dose; however, the low dose resulted in loss of sensitivity.
Conclusions PESP echocardiography is a useful and cost-effective method to identify viable myocardium in patients with multivessel coronary disease undergoing revascularization and is more sensitive and accurate than dobutamine infusion.
Left ventricular asynergies do not always represent an irreversible dysfunction of contractile machinery because the myocardium may be viable and intact and may maintain the potential for functional recovery. The term “hibernating myocardium” was first used by Rahimtoola1 to describe a state of persistent impaired myocardial and LV function at rest caused by reduced coronary blood flow that can be partially or completely restored to normal if the coronary blood flow is enhanced. It follows that the differentiation between viable and nonviable myocardium is a relevant issue in the current era of myocardial revascularization. The major objective of noninvasive imaging for the detection of myocardial viability is to assist and improve the selection of patients who would benefit most from revascularization. Myocardial viability may be detected as persistence of intermediary metabolism by positron emission tomography2 or as cell membrane integrity reflected by uptake of potassium analogues.3 Moreover, low-dose dobutamine infusion and PESP during 2D echocardiographic monitoring of LV function allow direct visualization of restoration of a normal contraction in asynergic myocardial regions. These methods are less costly and can be performed with high compliance at the bedside. The present study was performed to determine the accuracy of PESP, dobutamine, or their combination in identifying the reversible contractile dysfunction of hibernating myocardium and in predicting improvement after coronary artery bypass surgery.
We prospectively studied 84 consecutive patients with chronic multivessel coronary artery disease, all of whom were candidates for aortocoronary bypass surgery. Patients were selected if they met the following criteria: (1) demonstration of at least two major epicardial vessels with ≥70% stenosis by selective coronary angiography and the presence of wall motion abnormalities in at least two adjacent segments by 2D echocardiography, (2) suitability for surgical revascularization of all significant stenosis (≥70%) of the coronary arteries subtending the asynergic areas, (3) echocardiogram to assess wall motion and thickening in every LV myocardial segment, and (4) informed consent. Patients were excluded because of any of the following reasons: (1) angina during the echocardiographic study, (2) acute myocardial infarction or unstable angina within 6 months of the study, (3) LV aneurysm, (4) significant valvular heart disease, (5) history of sustained ventricular tachycardia or atrial fibrillation, (6) perioperative myocardial infarction, (7) early graft closure assessed by coronary arteriography at the time of follow-up echocardiography performed in all 84 patients, and (8) silent ischemia detected by 48-hour ambulatory ST-segment monitoring preceding preoperative and postoperative echocardiography because silent ischemia is a factor causing both stunned myocardium and loss of myocardial viability over time.4 5 The study was approved by the Institutional Review Board, and informed consent was obtained from all participants.
Of the 84 patients screened, 2 refused to participate, 7 (8.9%) had technically inadequate echocardiograms, 2 developed angina and ST changes during the echocardiographic study, 2 had early bypass closure, 7 (5 in the preoperative study and 2 in the postoperative study) had silent myocardial ischemia, 2 suffered intraoperative myocardial infarction, and 2 died perioperatively. The final group of 60 patients consisted of 54 men and 6 women, ranging in age from 40 to 72 years (mean, 58±9 years). Thirty-five patients (58.3%) had histories and ECG evidence of previous myocardial infarction (36 anterior and 24 inferior). Thirty-eight had three-vessel disease, and 22 had two-vessel disease. None of the patients included in this study had received a β-blocker, an inotropic agent, or a calcium channel blocker 48 hours before the echocardiographic assessment of myocardial viability; nitrates were stopped 12 hours before the test; and no patients received ACE inhibitors.
Dobutamine echocardiography was performed the same day as the surgical procedure, 1 hour after PESP. Echocardiographic examinations were performed by use of a Hewlett-Packard 77030A phased-array ultrasonoscope and a 2.5- or 3.5-MHz transducer; images were digitized on-line with an ECG R wave–triggered mechanism. A quad-screen, continuous-loop display was used to simultaneously compare resting with low and intermediate doses and recovery images (5 minutes after dobutamine infusion). Patients underwent continuous ECG monitoring. Dobutamine was infused intravenously by an infusion pump at 5 (low dose) and 10 (intermediate dose) μg·kg−1·min−1. The minimum duration of each stage of the infusion was 5 minutes. Blood pressure and heart rate were recorded at the end of each stage. Standard echocardiographic views were recorded in the left lateral position before, during, and for 5 minutes after dobutamine infusion. LV wall motion score, volumes, and LVEF were calculated at each stage of dobutamine infusion. After the test, the patient was observed with continuous ECG monitoring for an additional 15 minutes. Criteria for stopping the dobutamine infusion included hypotension, angina, significant ventricular or supraventricular arrhythmias, attainment of 85% maximal predicted heart rate, or a new or worsened abnormality in systolic wall thickening in at least two segments.
PESP was performed the same day as the surgical procedure, 1 hour before dobutamine testing. The basic heart rate was the patient’s own intrinsic sinus rate; PESP was recorded after an atrial induced extrasystole to obtain a completely noninvasive approach. Although the phenomenon is usually recorded after a ventricular extrasystole, it appears to be equally manifest after an atrial extrasystole.6 7 8 A quadripolar electrode catheter was passed through the nares into the distal esophagus. The lead was secured when the unipolar electrogram, recorded from the middle electrodes, exhibited the greatest amplitude and the most rapid deflection. In this position, consistent and constant atrial capture was achieved by means of a programmable stimulator with a pulse width and amplitude of 10 ms and 15 mA, respectively. A single atrial extrastimulus was delivered every 10th sensed, spontaneous sinus beat, and the induced extrasystole was progressively decreased by 10 ms, obtaining a coupling interval varying from 500 to 300 ms. The postextrasystole was then allowed to occur spontaneously, according to the patient’s intrinsic rhythm. During the procedure, LV dimensions were monitored by 2D echocardiography, and we considered for analysis only beats without significant changes in LV dimensions evaluated as LV area in the corresponding view during induction of PESP. This condition is necessary to avoid significant changes in LV preload associated with the compensatory pause after the extrasystole. A coefficient of variation of 5% was present for both interobserver and intraobserver variations. Thus, a 10% increase in LV dimensions represents the 95% confidence level for detecting significant changes.
PESP was repeated in parasternal long-axis, midventricular parasternal short-axis, apical four-chamber, and apical two-chamber views. PESP images with different coupling intervals, in each echocardiographic view, were arranged in a split-screen, continuous-loop display to be compared directly with the baseline. Regional systolic wall thickening was assessed according to the recommendation of the American Society of Echocardiography with a 16-segment model,9 and then WMSI was calculated. To study changes in LVEF, volumes were calculated at each coupling interval by a biplane, area-length method by use of apical four- and two-chamber views of postextrasystolic beats. For analysis, we considered only potentiated beats with similar duration of the interval between the extrasystole and postextrasystole for a given coupling interval.
PESP During Dobutamine Infusion
PESP, with a coupling interval ranging from 400 to 300 ms with 10-ms changes every 10th sinus beat, was repeated at the fifth minute of dobutamine (10 mg·kg−1·min−1) infusion. LV volumes, LVEF, and wall motion score were calculated for any given coupling interval.
LV function was studied by 2D echocardiography at rest (preoperatively and postoperatively) to assess changes induced by coronary bypass revascularization and during dobutamine infusion and PESP to predict preoperatively any improvement in regional systolic wall thickening after successful revascularization. Digitized echocardiograms were coded and read by two independent observers blinded to the patient’s identity and the order of the studies. Wall motion and myocardial thickening were analyzed by dividing the left ventricle into 16 segments, and a semiquantitative scoring system (1=normal, 2=hypokinesis, 3=akinesis, and 4=dyskinesis) was used.9 Agreement of interobserver analysis for segmental asynergy was seen in 98% of the segments visualized. Discrepancies were resolved by consensus with a third observer. Improved segmental wall motion during dobutamine infusion or PESP or at follow-up study was defined as endocardial excursion and wall thickening in akinetic or dyskinetic segments at baseline or normalization of endocardial excursion and wall thickening in hypokinetic areas at baseline. A change from dyskinesia to akinesia was considered to be unchanged segmental wall motion. Reversible dysfunction was defined as improved wall motion in at least two contiguous abnormal segments; this criterion was chosen to minimize the potential influence of tethering of an abnormal segment by adjacent normal or hyperkinetic segments. LV volumes were calculated by an ellipsoid biplane area-length method.10 EF was derived as EF=EDV−ESV/EDV, where EDV and ESV were the end-diastolic and end-systolic volumes. In our laboratory, the degree of interobserver and intraobserver correlations for serial measurements of LV area (r=.98 and r=.97, respectively) and of LV length (r=.98 and r=.96, respectively) is reasonable.11 The interstudy variability of resting LVEF was assessed by echocardiographic examination twice within half an hour and calculated by averaging the absolute differences between the two measurements. Changes in LVEF were considered significant if they were outside the 95% confidence limit of interstudy variability.
Follow-up echocardiograms were obtained in all 60 study patients who underwent successful and complete coronary bypass revascularization. All patients had echocardiographic follow-up 4 to 6 weeks after their procedures. At this time, coronary angiogram to exclude patients with early bypass closure and 48-hour ambulatory ST-segment monitoring to exclude patients with silent myocardial ischemia were repeated in the 64 patients enrolled after the preoperative evaluation who survived the surgical procedure without perioperative myocardial infarction. Postoperative resting WMSI, LV volumes, and EF were determined in a blinded fashion.
All data are expressed as mean±SD. Comparisons of continuous variables were made by one-way ANOVA and Bonferroni’s corrected t test. χ2 analysis was used to compare categorical data. A value of P≤.05 by two-tailed test was considered statistically significant. Linear regression analysis was used to correlate changes in LVEF with the corresponding coupling interval during PESP. Sensitivity of a test was calculated as true positive (number of asynergies correctly identified as reversible by the test) divided by the number of myocardial segments showing improvement after revascularization of the related stenotic coronary artery. Specificity was determined as true negative (number of asynergic segments correctly identified as not reversible) divided by the number of segments showing no improvement after revascularization of the related coronary artery. Accuracy was determined as true positive plus true negative divided by the total number of asynergies.
Preoperative and Follow-up Studies
A total of 960 myocardial segments were analyzed in the 60 patients. Heart rate (69±18 versus 74±16 bpm, P=NS), systolic blood pressure (140±14 versus 142±12 mm Hg, P=NS) and diastolic blood pressure (86±6 versus 84±7 mm Hg, P=NS) at the moment of the preoperative and postoperative studies did not differ. Resting preoperative echocardiographic examinations detected 115 dyskinetic (12%), 499 akinetic (52%), 135 hypokinetic (14%), and 211 normal segments (22%). Systolic wall thickening and contraction improved after bypass myocardial revascularization in 404 segments (54%): 340 (84%) became normokinetic and 64 became hypokinetic. The remaining 345 segments (46%) did not improve and were considered irreversible asynergies. Analysis of all individual myocardial segments revealed a different capability of asynergies to improve contractile function after bypass: 129 of 135 hypokinetic (96%), 269 of 499 akinetic (54%), and only 6 of 115 dyskinetic segments (5%) showed improved systolic wall thickening. The regional WMSI improved significantly after coronary artery bypass grafting (from 2.26±0.29 to 1.49±0.26, P<.001; Fig 1⇓). LVEDVI reduced from 84±21 to 72±24 mL/m2 (P=.003), and LVEF improved from 48±10% to 59±8% (P<.001).
Dobutamine stress echocardiography correctly identified contractile reserve in 348 of the 749 asynergic segments (46%). The dobutamine dose at which regional wall thickening first showed improvement was variable: 216 (62%) asynergic segments increased at 5 mg · kg−1 · min−1 for 5 minutes, and 132 increased at 10 mg · kg−1 · min for 5 minutes. In 9 patients (15%), 24 myocardial segments improved after the first dobutamine infusion and did not improve after the second infusion.
Mean LVEF increased from 48±10% to 54±8% (P<.001) after 5 mg · kg−1 · min−1 of dobutamine infusion per 5 minutes and to 58±12 (P<.001) after 10 mg · kg−1 · min−1 of dobutamine infusion per 5 minutes, respectively. During the low-dose test, LVEDVI did not change significantly (84±21 versus 80±20, P=NS), and heart rate increased from 69±18 to 82±16 bpm (P<.001). During the intermediate-dose test, LVEDVI tended further to reduce but not significantly (78±22 mL/m2, P=NS), and heart rate increased (86±18 bpm; P<.001).WMSI for the group at the completion of dobutamine test improved from 2.26±0.29 to 1.82±0.24 (P<.001; Fig 1⇑).
Specifically, 414 myocardial segments manifested contractile reserve during dobutamine infusion, 348 of which subsequently showed improved regional wall thickening after coronary revascularization. In contrast, 279 of 345 myocardial areas that had no significant improvement during dobutamine infusion failed to improve after revascularization. Thus, the sensitivity of the test was 86.1%, the specificity was 80.8%, and the accuracy in predicting reversibility of asynergies after bypass was 83.7%.
PESP adequately predicted the reversal of contractile dysfunction in 372 of the 749 asynergic segments (49.6%). The number of asynergic myocardial areas that first reversed the baseline contractile dysfunction progressively increased as the interval between the normal systole and the extrasystole became shorter: 22 asynergic segments (6%) improved with a coupling interval of 500 to 450 ms, 37 asynergies (10%) showed improvement of myocardial function between 450 and 400 ms, 204 segments (55%) improved between 400 and 350 ms, and 109 (29%) improved between 350 and 300 ms. All these myocardial segments reversed their contractile dysfunction at a coupling interval of 400 to 300 ms, independent of the time of first improvement. No myocardial segments showed deterioration of contraction during PESP induction. LVEDVI in the postextrasystolic beats used for analysis did not differ from baseline values (88±29 versus 84±21 mL/m2, P=NS), whereas LVEF increased significantly (68±10% versus 48±10%, P<.001). The maximum increase in LVEF (Fig 2⇓) by PESP was significantly greater than the maximum increase by both low- and intermediate-dose dobutamine infusion (P<.001 for both). A significant negative linear correlation (Fig 3⇓) existed between potentiated LVEF and the corresponding coupling interval (r=−.5962, P<.001). WMSI for the entire group improved significantly by PESP from 2.26±0.29 to 1.64±0.29 (P<.001; Fig 1⇑). PESP determined a significantly greater decrease in WMSI than dobutamine (P<.001). Specifically, 421 myocardial segments manifested recruitable contractile reserve by PESP, 372 of which subsequently showed improved regional wall thickening after bypass. In contrast, 296 myocardial areas of 345 segments without significant improvement by PESP failed to improve after myocardial revascularization. Thus, the sensitivity of the test was 92%, the specificity was 85.7%, and the accuracy in predicting reversibility of regional myocardial dysfunction after bypass was 89.2%.
Prolongation of the coupling interval because of spontaneous intranodal delay did not allow us to consider for analysis 142 of 5040 stimulations (2.8%). No complications occurred during PESP procedure; the total mean duration of the study was 28 minutes.
Association of Dobutamine Infusion and PESP
The association of dobutamine and PESP correctly predicted the presence of a reversible contractile dysfunction in 370 of the 749 asynergic myocardial areas (49.3%). Specifically, 425 myocardial asynergic segments showed significant improvement during PESP associated with dobutamine infusion, 370 of which subsequently improved the pattern of contraction after coronary artery bypass revascularization. However, 290 of 324 asynergic areas that did not significantly improve during the combined test failed to improve after revascularization. Thus, the sensitivity was 91.5%, the specificity was 84.0%, and the accuracy in predicting the postbypass reversibility of asynergies was 88.1%. WMSI reduced significantly from 2.26±0.29 to 1.69±0.27 (P=.006). This reduction was significantly greater than that induced by dobutamine infusion alone (P=.006), but it did not differ from changes obtained by PESP (P=NS). In 9 of 60 patients (15%), 24 asynergic areas improved after the first infusion and did not improve after the second one; PESP restored a normal contraction in 20 of these areas (83.3%).
LVEF significantly increased from 48±10% to 66±9% (P<.001). The improvement in LVEF by PESP during dobutamine infusion was significantly greater than the increase by dobutamine alone (P<.001), but it did not differ from changes induced by PESP alone (P=NS).
Of the 2640 stimulated beats, 64 (2.4%) were not considered for analysis because of spontaneous intranodal delay.
In the current era of myocardial revascularization, the accurate distinction of viable from nonviable myocardium in patients with coronary artery disease is an issue of increasing clinical relevance. The prospective identification of potentially reversible myocardial dysfunction may provide significant prognostic information because improvement in LV function after revascularization is associated with improved survival.12 13 14 15 16 17
This study shows that echocardiographic assessment of a reversible contractile dysfunction in hibernating myocardium by dobutamine infusion or PESP is predictive of improvement after coronary bypass. The results of both methods are highly acceptable for clinical application. Nevertheless, PESP may be more useful because it has higher sensitivity (92% versus 86%, P=.009) and accuracy (89.2% versus 83.7%, P=.001), whereas specificity is similar for both methods. The combination of the two methods does not improve the capability of PESP alone to predict restoration of contractile function after revascularization.
Several observations may explain the superiority of PESP. In this study, 15% of patients showed deterioration of regional myocardial function at an intermediate dose of dobutamine after an early improvement at a low dose. However, low-dose dobutamine infusion is able to identify only 62% of reversible myocardial asynergies detected by the overall test. Low doses of dobutamine reduce the risk of inducing myocardial ischemia, but the intensity of inotropic stimulation is not enough to restore a normal contractile function in hibernating myocardium in most patients. The possibility of a dobutamine-induced ischemia has also been stressed in previous studies.18 19 The susceptibility of hibernating myocardium to ischemia and the large variability in the intensity of inotropic stimulus necessary to restore contractile function may explain the results of PESP. In fact, inotropic stimulation by PESP is of increasing intensity because it reduces the coupling interval without the risk of inducing myocardial ischemia because it is instantaneous. Interestingly, the power of inotropic stimulus by PESP was enough to improve myocardial function in most LV areas (83.3%) with an ischemia-induced deterioration at intermediate doses of dobutamine. A potential limitation of PESP may derive from the modality of transesophageal stimulation that requires careful control of the effective coupling interval. Spontaneous delay of intranodal conduction may prolong the value of the programmed coupling interval and reduce the expected intensity of inotropic stimulus. In our study, this occurred in a small percentage (2.6%) of 7680 extrasystoles induced during PESP studies. However, echocardiographic monitoring of LV avoids some important limitations of PESP during contrast ventriculography, which offers a minimal number of beats for analysis and may cause changes in LV contractility and load by contrast medium.
Other methods of detecting viable myocardium such as positron tomography and thallium allayed imaging have also been shown to predict recovery of function after revascularization.8 9 These methods that do not allow direct visualization of contractile improvement have the potential of indicating the presence of viability even in the absence of residual contractile reserve, as in the presence of small islands of viable myocytes within a predominantly scarred region.20
In conclusion, echocardiography during dobutamine infusion or PESP can accurately identify the presence of viable hibernating myocardium in patients with coronary artery disease and may be helpful in predicting functional recovery after coronary artery bypass. Even though the best approach depends on the individual patient and the expertise of a particular institution in a specific technique, PESP is more useful than dobutamine in allowing maximal contractile recruitment without inducing ischemia.
Selected Abbreviations and Acronyms
|LVEDVI||=||left ventricular end-diastolic volume index|
|WMSI||=||wall motion score index|
- Received July 1, 1996.
- Revision received February 18, 1997.
- Accepted February 24, 1997.
- Copyright © 1997 by American Heart Association
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