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Ann Thorac Surg 2004;78:135-141
© 2004 The Society of Thoracic Surgeons
a Department of Cardiology and Cardiac Surgery, "G. D'Annunzio" University of Chieti, Chieti, Italy
Accepted for publication December 2, 2003.
* Address reprint requests to Dr Zimarino, Ospedale San Camillo de Lellis, University of Chieti, Via Forlanini 50-66100, Chieti, Italy
e-mail: m.zimarino{at}unich.it
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Abstract |
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METHODS: Myocardial function was evaluated in 92 patients by intraoperative transesophageal echocardiography during MIDCABG.
RESULTS: Wall motion score index increased during LAD occlusion (p < 0.00l) and reverted after LAD reopening (p < 0.001 versus occlusion and p = not significant versus baseline). The change in wall motion score index (occlusion versus baseline) was higher in patients with multivessel disease (p < 0.05) and in patients with LAD Thrombolysis in Myocardial Infarction study classification flow grade 2 or less without collateral circulation (p < 0.05). Myocardial stunning was documented in 12 patients (13%). The 5-year adverse event rate (including death, myocardial infarction, and revascularization) was 12%. By multivariate Cox regression analysis, multivessel disease, but not perioperative ischemia or stunning, was the only predictor of event-free survival.
CONCLUSIONS: During MIDCABG anterior wall dysfunction is transient, with prompt recovery after completion of the anastamosis in most cases; myocardial stunning can be documented in a minority of patients. Flow either antegrade or retrograde in the LAD territory plays a protective role against the development of ischemia. Multivessel disease, but not perioperative ischemia or stunning, predicts long-term event-free survival.
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Introduction |
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In the present study we used intraoperative transesophageal echocardiography (TEE) to assess the effects of prolonged LAD occlusion on myocardial dysfunction during MIDCABG, and evaluated the impact of myocardial ischemia on long-term outcome. We also sought to test the protective role of collateral circulation on myocardial ischemia in this setting.
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Material and methods |
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Surgical technique
As previously described [2], the chest was opened through a left anterior small thoracotomy, ribs were retracted, and the pericardium was incised vertically. The left internal mammary artery was harvested and, in the majority of cases, skeletonized. After systemic heparinization (1 mg/kg), the left internal mammary artery was divided, injected with a papaverine solution and its flow and quality carefully evaluated. The LAD was then occluded proximally and distally with the aid of a small piece of silicone tubing in order to avoid any direct compression. A mechanical stabilizer was used to reduce movements of the artery. The LAD was then incised, and the anastomosis with the left internal mammary artery performed.
The MIDCABG was performed in 39 subjects (43%) with multivessel coronary artery disease as a "functionally adequate" myocardial revascularization: in 15 cases only minimal or no viable myocardium was detected in areas other than that supplied by the LAD, in 18 cases a diffuse disease of distal branches was present, and in 6 cases the disease of non-LAD coronary arteries was judged not relevant.
Coronary angiography
Coronary angiograms were reviewed by two independent observers (M.Z. and M.D.M.). The projection using the most severe coronary narrowing was selected. Using the guiding catheter as a calibration standard, a caliper-assisted measurement of minimal lumen and reference diameters was performed, and the percent lumen diameter stenosis calculated [7]. Multivessel coronary disease was defined as more than 50% stenosis in one or more vessels remote from the LAD.
The antegrade LAD flow was graded with the use of the Thrombolysis in Myocardial Infarction (TIMI) study classification without knowledge of patient data [8]. In brief, grade 0 = no antegrade flow; grade 1 = minimal incomplete perfusion of contrast medium beyond the point of occlusion; grade 2 (partial perfusion) = complete but delayed perfusion of the distal LAD bed; grade 3 (complete perfusion) = antegrade flow to the entire distal LAD bed at a normal rate.
The angiographic collateral vessel filling was graded by visual analysis according to Rentrop and associates [9]: 0 = absent collateral circulation; 1 = filling of collateral vessels without any epicardial filling of the LAD; 2 = partial epicardial filling of the LAD by collateral vessels; 3 = complete epicardial filling of the LAD by collateral vessels.
Grading of the antegrade LAD flow and collateral vessels was performed independently by the two angiographers, and a consensus was reached when they differed.
Echocardiographic imaging and analysis
All study patients underwent a complete TTE the day before surgery and on postoperative day-3 using an ATL Apogee Cx 200 (Interspec-ATL, Bothell, WA) with a 3.5 MHz probe. Intraoperative TEE was performed with a 5 MHz multiplane probe. The TEE imaging was performed after anesthesia induction (baseline), during the period of anastamosis (occlusion), and during maximum recovered wall motion within 60 minutes after the anastamosis was completed (recovery). The TEE imaging included the four-chamber, two-chamber, and long-axis views (in sequence) followed by the transgastric short- and long-axis views; the probe was manipulated in order to avoid foreshortening of the left ventricular apex.
All TTE and TEE studies were reviewed off-line by two experienced echocardiographers (S.G. and M.D.F.) masked to patients data and to the study sequence. Concordance between independent readings by the two operators was previously tested (k = 0.90 for TTE and 0.91 and for TEE). Regional wall motion was indexed according to the 16-segment model proposed by the American Society of Echocardiography [10, 11]: normal = 1; hypokinetic = 2; akinetic = 3; and dyskinetic = 4. Left ventricular wall motion score was obtained by adding the scores of all 16 segments. A wall motion score index (WMSI) was calculated by dividing the global score by the number of segments analyzed. According to this scoring system, a higher score indicates worse function. To quantify the amount of jeopardized myocardium, the variation between occlusion and baseline WMSI (
WMSI) was calculated.
In cases where intraoperative TEE documented WMSI at recovery more than baseline, myocardial stunning was considered if function normalized at day 3 TTE [12]. Myocardial damage was defined if function was persistently deteriorated at day 3 TTE.
Among the 1,472 myocardial segments identified at intraoperative TEE, 1,451 segments (98.6%) could be evaluated at each stage of the procedure; 21 segments (1.4%) were not adequate for wall motion analysis: apical septal, apical lateral, and apical anterior segments in 4 cases, mid lateral in 3 cases, and apical inferior, mid anterior, and basal anterior in 2 cases. Particular care was taken to avoid misinterpretation due to surgeon's manipulation of the stabilizer: the placement of this device was indicated during tape recording, and the occlusion study was performed usually after the completion of the anastomosis and the stabilizer removal, before LAD reopening.
Clinical events and follow-up
Major adverse cardiovascular events were defined as death, nonfatal myocardial infarction (prolonged chest pain with a documented rise in CK-MB > 3 times the upper normal laboratory limit, or development of new Q waves), and all new revascularization procedures, whether percutaneous or surgical. All events were source-documented and adjudicated by consensus of two reviewers (G.V. and G.D.G).
Clinical follow-up was carried-out on all 92 study patients (100%) by either telephone contacts or office visits within 1 month after MIDCABG and every 6 months thereafter up to 7 years.
Statistical analysis
Continuous data were expressed as mean ± SD and compared by the Student t test. Discrete variables were expressed as counts and percentages and compared by the Fisher's exact test. Analysis of variance for repeated measures with the Bonferroni's correction for posthoc analyses tested differences in WMSI during baseline, occlusion, and recovery.
Kaplan-Meier life-table analysis was used to calculate event-free survival, and significance was here tested by the log-rank test.
Cox multivariate regression analysis was used to model independent predictors of long-term major adverse cardiac events. Variables included in the model were age, sex, diabetes, hypertension, previous myocardial infarction, previous CABG, unstable angina, multivessel disease, left ventricular ejection fraction, WMSI, and the presence of myocardial stunning or damage after MIDCABG.
Statistical analysis was performed with the use of the SPSS package (release 7.5 version; SPSS, Chicago, IL). Significance was established at the level of p less than 0.05 except for posthoc analyses (p < 0.016 = 0.05/3).
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Results |
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Procedural results
The LAD occlusion lasted 22 ± 6 minutes. Myocardial dysfunction occurred 3.6 ± 2.6 minutes after LAD occlusion; myocardial recovery was noted 4.2 ± 2.1 minute after the completion of the anastomosis. No patient needed hemodynamic support with drugs or intraortic balloon pump during MIDCABG nor thereafter during the hospital stay. Peak CK and CK-MB release were 756 ± 413 IU/mL and 29 ± 26 IU/mL, respectively.
Overall wall motion analysis
The WMSI increased from 1.34 ± 0.32 at baseline to 1.48 ± 0.36 during occlusion (p < 0.001), indicating a deterioration of left ventricular function during occlusion. The WMSI completely reverted after LAD opening (1.30 ± 0.32, p < 0.001 versus occlusion; p = not significant versus baseline). When compared with both baseline and recovery, wall motion score during occlusion was significantly worse during occlusion in mid anteroseptal, mid septal, apical septal, apical lateral, and apical anterior segments (Fig 1).
There was no significant deterioration in wall motion in any of the other segments throughout the study, even in patients with multivessel disease. In 54 patients (59%), a deterioration of contractile function during occlusion occurred in two or more myocardial segments.
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Taking into account both antegrade and retrograde flow in the LAD territory, WMSI was significantly higher among patients with TIMI flow grade 2 or more and absent collateral circulation when compared with subjects with either TIMI flow grade 3 or the presence of significant (Rentrop 
1) collateral circulation (p < 0.05; Fig 3).
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Baseline characteristics in patients with myocardial stunning were similar to the overall population; multivessel disease was present in 6 of 13 patients (46%, p = not significant versus patients without myocardial stunning). The LAD occlusion time was 23 ± 8 minutes, similar to the remaining patients (22 ± 7 minutes, p = not significant). Subjects in this cohort showed a larger amount of jeopardized myocardium during MIDCABG: WMSI was significantly higher (0.31 ± 0.15) when compared with patients showing a normalized or improved myocardial function at the end of surgery (0.12 ± 0.13, p < 0.001). Peak CK-MB release was 24 ± 9 IU/mL, similar to subjects with myocardial recovering early after MIDCABG (29 ± 27 IU/mL, p = not significant).
In-hospital outcome
There were no in-hospital deaths. Three patients (3.3%) had a myocardial infarction during the hospital stay; in none of them persistent myocardial dysfunction at the end of MIDCABG (recovery WMSI greater than baseline) was detected. These patients underwent diagnostic angiography the following week. In 2 of them a coronary angioplasty was performed, with stent implantation in the right coronary artery in 1, and in the circumflex artery in the other. One patient had a patent left internal mammary artery and a previously stenotic proximal LAD was found occluded; the remaining coronary circulation was normal. One patient with postoperative graft bleeding required an emergency open thoracotomy, but total patency of the conduit was found during repeat surgery by Doppler and 3 days later confirmed by angiography.
Atrial fibrillation developed in 5 of 88 patients with preoperative sinus rhythm (6%); subjects who had atrial fibrillation had similar baseline and procedural characteristics when compared with the remaining patients with preoperative sinus rhythm.
Follow-up
The mean follow-up was 66 ± 26 months (range, 41 to 86; median, 63). During the follow-up, 3 patients died. One patient experienced recurrent chest pain 4 months after MIDCABG; angiography showed an occluded left internal mammary artery, and a percutaneous angioplasty with stent deployment in the LAD was performed. One patient underwent stent implantation on the left circumflex and the right coronary artery 30 months after surgery.
After 5 years, follow-up was completed in 65 patients (71%). The overall survival was 95%; major adverse cardiac events were documented in 8 subjects (12%).
The actuarial event-free survival was similar in patients with postoperative myocardial stunning (92% ± 8%) compared with patients with myocardial function found unchanged or improved after MIDCABG (91% ± 3%, p = not significant). The 5-year actuarial event-free rate for patients with a relevant amount of jeopardized myocardium during MIDCABG (at least 2 ischemic myocardial segments, WMSI 0.125) was similar to patients with minimal ischemia during MIDCABG (91 ± 4 versus 92% ± 4%, p = not significant).
The probability of event-free survival was significantly lower for patients with multivessel disease (82% ± 6%), when compared with subjects with isolated LAD disease (98% ± 2%, p = 0.0072; Fig 4).
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Comment |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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Myocardial ischemia and LAD flow
Intraoperative TEE documented that myocardial dysfunction in patients submitted to MIDCABG is confined to distal LAD territories. This may be because of the presence of developed collaterals in more than one third of patients and to the distal location of the occlusion site. As already reported by Brown and colleagues [5] in a small series of patients, systolic dysfunction was more significant with lesser degrees of coronary artery stenosis, implicating lesser development of collateral circulation or of preconditioning. Our data extend these observations, showing that anterior wall motion worsened if impaired antegrade flow was present before the operation or if collaterals were poorly developed.
In a series of 17 patients undergoing MIDCABG for severe LAD stenosis, ischemic preconditioning with brief episodes of coronary occlusion failed to preserve myocardium from the development of ischemia during the anastomosis [13]. It therefore appears that chronic physiologic adaptations of the coronary circulation to the stenosis exert a better protection on myocardial systolic function than the induction of transient ischemia during surgery.
Recently, Menon and associates [14] tested the effectiveness of temporary intraluminal shunting during MIDCABG: this technique prevented myocardium from systolic dysfunction, that lasted 30 minutes after removal of the occlusive system was completely reversible. We deliberately tried to minimize the manipulation of LAD artery, however, as iatrogenic lesions are not so infrequently documented after MIDCABG [15].
Myocardial stunning
Postoperative stunning commonly occurs after cardiac surgery [16, 17]. In our study, myocardial stunning was identified in a minority of cases (1.8% of segments analyzed and 13% of patients) and was associated with a larger amount of jeopardized myocardium, indicating that recovery after MIDCABG needs more than 1 hour to be completed, when transient ischemia is of sufficient magnitude. However, myocardial stunning had no impact on either in-hospital or long-term outcome. That lack of impact might be due to the limited number of patients studied, in a relatively low-risk population, in which only eight major adverse cardiac events were recorded, mainly revascularization procedures in territories other than LAD artery. This issue needs verification in a larger population.
MIDCABG in patients with multivessel disease
The leading indication for MIDCABG surgery is single-vessel disease with chronic occlusion or recurrent restenosis of the LAD artery. Promising results obtained after the initial experience encouraged the inclusion of patients with multivessel disease and significant concurrent medical illnesses for whom cardiopulmonary bypass entails a relevant risk [3, 4]. Whenever feasible, off-pump CABG reduces in-hospital morbidity without affecting midterm outcome compared with traditional surgery with cardiopulmonary bypass [18]. A strategy of "functional" revascularization with MIDCABG conceptually differs from complete anatomical bypass grafting. Our results show that patients with multivessel disease develop a larger amount of transient ischemia during surgery compared with patients with single LAD disease, without increased in-hospital complications. During the follow-up, however, the extent of coronary artery disease was the only determinant of adverse outcome.
Limitations
We acknowledge several limitations of the current study: intraoperative TEE was performed in a selected series of patients; however, baseline clinical and angiographic characteristics of our study patients were comparable to our overall MIDCABG population. Data are also lacking on the correlation between preexisting inducible ischemia and the extent of myocardial dysfunction during MIDCABG; this gap of knowledge needs to be addressed by further studies. Another limitation is that troponin enzymes were not systematically available at the time of the study.
Myocardial contrast echocardiography is more accurate than coronary angiography in the detection of collateral circulation [19] and could have added insights into the mechanism of protection against ischemia. Also, the metabolic effects of coronary occlusion were not assessed in the present study. The use of a measure of systolic function more sensitive than WMSI, such as absolute (in mm) or percent myocardial thickening could have further detailed the analysis. Moreover, the study did not address diastolic dysfunction, which may precede and persist longer than systolic dysfunction accompanying acute ischemia.
The limited number of the study population could be responsible for a beta error, preventing the detection of additional risk factors (such as the extent of transient ischemia) for long-term adverse events. Therefore, although our study population is representative of a larger cohort, enthusiastic reports of the final outcomes of this surgical technique must be viewed cautiously and compared with those of conventional surgery in a larger population only after adjustment for baseline variables [20].
In conclusion, within durations of ischemia of the LAD territory limited to 30 minutes, MIDCABG does not apparently cause persistent wall motion abnormalities. Although myocardial stunning can be documented in a minority of patients, this is transient. Intraoperative TEE can document a depression of contractile function in the anterior territory, to an extent related to the severity of coronary artery disease and the degree of epicardial coronary flow. Long-term events, however, are not related to the severity of transient ischemia during LAD occlusion. A reduced long-term event-free survival was related to the extent of coronary artery disease, thus constituting a strong argument for complete revascularization at the time of the initial bypass surgery.
Larger studies are needed to ascertain the effectiveness of MIDCABG as a "functional" revascularization in patients with multivessel coronary artery disease compared with traditional bypass surgery.
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