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© 2003 European Association of Cardio-Thoracic Surgery
Revascularization of dysfunctioning myocardium: differential prognostic effects of coronary artery bypass grafting and percutaneous transluminal coronary angioplasty in patients with three-vessel disease and mostly viable myocardium
a CNR Institute of Clinical Physiology, Via Moruzzi 1, Pisa, Italy
* Corresponding author. Nuclear Cardiology, The CNR Institute of Clinical Physiology, Via Moruzzi 1, 56100 Pisa, Italy. Tel.: +39-050-3152153; fax: +39-050-3152151 Received September 18, 2002; received in revised form March 21, 2003; accepted March 24, 2003
In patients with left ventricular dysfunction, multivessel coronary disease and viable myocardium, little is known on the differential prognostic effect of coronary artery by pass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). To this purpose, 177 patients with previous myocardial infarction, three-vessel coronary disease and an  underwent CABG (group A, 114 patients) or PTCA (group B, 63 patients). Viability was demonstrated by maintained Thallium-201 uptake in more than 70% of left ventricle in 95/114 and 51/63 patients of groups A and B, respectively. Revascularization was greater in the CABG group (2.9±1.2 graft/patient) as compared to the PTCA group (1.3±1.2 treated vessel,  ). Intraoperative mortality was 6.7 and 6.3% in groups A and B, respectively. At 6 months, viability was highly predictive of improvement of symptoms and wall motion abnormalities. Survival at 4 years was 90% in CABG and 92% in PTCA patients with maintained viability, while cumulative hard event rates showed an event-free survival of 86 and 76% in groups A and B, respectively (log rank: 0.0035). In patients with three-vessel coronary disease, low EF and mostly viable myocardium, coronary revascularization was associated with a favourable 4-year survival, even if CABG was superior to PTCA in reducing cumulative events.
Key Words: Surgical revascularization; Percutaneous transluminal coronary angioplasty; Myocardial viability; Multivessel disease
Coronary artery by pass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) have been developed in the past decades as alternatives to medical therapy for the treatment of patients with coronary artery disease [1,2]. The individual results of matched trials as well as of a meta-analysis [3,4] failed to show any significant difference in overall mortality between CABG and PTCA, with the exception of the ERACI II study [2]. This randomized study revealed that in patients with an ejection fraction (EF) higher than 30%, multivessel disease PTCA with stent resulted in a significantly lower incidence of event during hospitalization and at 30 days when compared to CABG. Moreover, previous studies [3,5] reported that the extent and the specific site of coronary lesion, as well as the type of revascularization were independent predictors of survival. These results were partially questioned by a recent study [6] that showed no differences in 7-year survival between an initial strategy of PTCA or CABG among patients with three- or two-vessel disease involving the proximal left anterior descending (LAD) coronary artery. However, despite these conflicting results, few information is available about the comparison between CABG and PTCA in high-risk patients, characterized in terms of viability and recovery of regional wall motion. In this field, studies focusing on the prognostic impact of CABG as well as PTCA as compared with medical treatment, showed the positive predictive value of viability assessment in revascularized patients [7,8]. The goal of the present study is to evaluate the prognostic impact of revascularization, achieved either by CABG or PTCA in a population of consecutive patients with ischaemic left ventricular dysfunction and three-vessel disease with and without viable myocardium.
From a data base of 1045 consecutive patients who were scheduled for revascularization between 1 January 1995 and 31 December 1997 a subgroup of 177 patients with previous myocardial infarction, three-vessel disease and an angiographic were selected. In all patients coronary angiography were obtained within 1 month from echocardiographic and scintigraphic studies. The patient groups were further subdivided on the basis of their Thallium-201 scan, into those with a majority of viable myocardium and those with a dominance of scar. Patients with recent myocardial infarction (<3 months), valvular heart disease or cardiomyopathies, previous CABG or PTCA were excluded from the study. 2.1. Echocardiography Baseline echocardiography was performed at the enrolment and 6 months after revascularization. The left ventricle was divided in a 16-segment model [9]. Segmental wall motion was graded as: normal (score=1), hypokinetic (score=2), akinetic (score=3), dyskinetic (score=4). A wall motion score index (WMSI) was derived by dividing the sum of individual segment scores by the number of interpretable segments [9].2.2. Thallium-201 scintigraphy All patients underwent a rest–redistribution Thallium-201 study, as previously described [10]. Delayed images were quantitatively analyzed for maintained Thallium-201 uptake using a bull's eye plot based on the same 16-segment model used for echocardiography. To define viable ( 54%) or necrotic (<54%) segments, Thallium-201 uptake was assessed in each of the 16 segments using a cut-off of 54% of the peak. The amount of viable myocardium was assessed according to ROC curve. 2.3. Follow-up Six-month after enrolment, all patients were reassessed by echocardiography for WMSI and evaluated for symptoms by interview and examination. Survival status was followed for additional 48 months by contacting all patients or next of kin by telephone. Cardiac events during late follow-up were defined as cardiac death and cardiac transplantation for refractory heart failure.2.4. Statistics Data were expressed as mean±1 standard deviation. A P value of <0.05 was considered significant. Kaplan Meier survival estimates were used. Significant differences in survival ( by two tailed tests) between CABG and PTCA groups were tested by the Log Rank test. To assess the association of each variable with survival while controlling for the effects of the other variables, a Cox proportional-hazard regression was performed. This constituted the multivariate analysis. For the regression model, a forward stepwise procedure was used to select the significant variables among the following: age, sex, diabetes, hypertension, presence of angina, NYHA class, EF, maintained viability as indicated by the ROC curves, site of LAD lesion and echocardiographic WMSI. The significant level to enter the model was  . For the purpose of estimating coefficients in the regression model, follow-up was truncated at 48 months after enrolment for all patients. ROC curve was used to determine this ‘optimal’ cut-off value for the prediction of late events, with respect to the percentage of maintained Thallium-201 uptake at rest in the 16 segments: when 11/16 segments had maintained Thallium-201 uptake, about 70% of the left ventricle was viable (Fig. 1).
Out of 177 enrolled patients, 114 were revascularized by CABG (group A), while 63 by PTCA (group B). Baseline characteristics of the two groups are presented in Table 1.
Group A: The average number of by pass grafts was 2.9±1.4. All patients received an internal mammary graft on the LAD. Group B: Twenty-two out of 63 underwent PTCA as indicated by the surgeon because of high estimated operative risk; in 26/63 patients the referring cardiologist suggested PTCA as first choice procedure while 15 patients declined CABG. The average number of dilated vessel was 1.4±0.8 and all patients were revascularized on the LAD (10/63 also by stenting). In 15/63 patients two vessels were treated: LAD and right coronary artery (RCA) in nine patients and LAD and left circumflex (LCX) coronary artery in six patients. 3.1. Myocardial viability and regional wall motion According to the ROC curves, 95/114 and 51/63 patients of groups A and B showed mostly viable myocardium, while the remaining had dominance of scar in dyssynergic segments. The mean number of viable segments at Thallium-201 was 12.8±0.9 and 13.1±1.2in groups A and B, respectively, while the resting WMSI was 2.4±0.3 and 2.3±0.7 in the two groups (P=ns).3.2. In hospital mortality In hospital mortality was 8/114 (6.7%) in group A and 4/63 (6.3%) in group B (P=ns). Mortality was reduced to 5.2% (five patients) and 4% (two patients) in groups A and B, respectively, when only patients with mostly viable myocardium were considered.Finally, the few revascularized patients of groups A and B with mostly necrotic myocardium had an intraoperative mortality of 17% (3/17) and 16% (2/12), respectively. 3.3. Short-term follow-up At 6 months, in patients of group A with maintained myocardial viability, WMSI decreased from 2.4±0.3 to 1.7±0.5 , and all patients referred the absence of anginal symptoms and the improvement of effort dyspnoea. In viable patients of group B, WMSI decreased from 2.5±0.7 to 1.8±0.4 and four patients referred the persistence of symptoms. For this reason, these four patients with effort angina were submitted to new angiography and revascularization. In patients of groups A and B with dominance of scar, WMSI after revascularization was not statistically different from the control value (2.9±0.9 and 2.8±0.7 before revascularization versus 2.8±1.0 and 2.9±0.9 after, P=ns, for all values). All but two patients with mostly necrotic myocardium did not report any improvement of effort dispnoea. 3.4. Long-term follow-up All patients were treated with combinations of drugs necessary to individual clinical conditions. During the follow-up, 12 deaths occurred for cardiac causes (seven in group A and five in group B) and one patient of group A had heart transplantation.When considering only patients with mostly viable myocardium, six cardiac deaths occurred during the follow-up (four in group A and two in group B). Two patients in group A and two in group B experienced a non-fatal myocardial infarction (related to a previously revascularized vessel). In group A, two patients underwent PTCA, one on an internal mammary graft and one on a venous graft, 6 and 8 months following surgery. In group B, two patients received CABG (in addition to mitral valve replacement) and four were re-submitted to PTCA and stenting, from 6 to 10 months following the first one. 3.5. Univariate and multivariate analysis Univariate analysis indicated that diabetes ( ,  ), absence of myocardial viability (,  ), EF ( ,  ) and WMSI ( ,  in groups A and B, respectively, for all the categories) were correlated with the worst prognosis. Multivariate regression analysis was detailed in Table 2.
3.6. Kaplan Meier survival curves Fig. 2 shows the Kaplan Meier curves of group A and B patients.
This study compares short- and long-term survival following CABG and PTCA in patients with significant ischaemic left ventricular dysfunction and dominance of myocardial viability. The discussion will focus on the outcome in the two groups, on the role of LAD revascularization, on intraoperative complications and on the impact of myocardial viability in the decision making of these patients. 4.1. Outcome: short-term follow-up This study suggests that, in presence of ischaemic left ventricular dysfunction and multivessel disease, the extent of viable myocardium is an important predictor of early death in patients revascularized with CABG as well as with PTCA. In presence of maintained myocardial viability, revascularization can be performed with acceptable risk of intraoperative mortality, while in presence of mostly necrotic myocardium it should be carefully avoided. Moreover, mostly viable myocardium, at least 70% of the left ventricle as suggested by these findings, was highly predictive of improvement of symptoms and wall motion abnormalities after revascularization.4.2. Outcome: long-term follow-up This study documents a favourable and similar long-term survival in CABG and PTCA groups, especially if considering only patients with mostly viable myocardium. The absence of a significant difference in cardiac mortality between the two groups at 4 years, despite the marked difference in the number of revascularized vessels, was a very interesting result and confirmed previous observations [2,6]. One of the possible explanation of this result for the PTCA group might correlate with the high prevalence (100%) of LAD revascularization and with the presence of significant residual viability in this territory.Two recently published studies [11,12], performed in patients with single vessel proximal LAD disease revascularized either by PTCA and left internal mammary artery graft, showed that the risk of cardiac death was similar and very low in the two groups. Moreover, the left internal mammary artery bypass alone reduced the incidence of re-infarction and repeated procedures. The analysis of a subgroup of Bypass Angioplasty Revascularization Investigators (BARI) population [6] with multivessel disease showed similar short- and long-term outcome in the surgical as well as in the PTCA group. These data support our results, even if the populations are not quite comparable and chosen according to different inclusion criteria. In the present study, the incidence of restenosis did not differ from that reported in the literature for less selected patients [1,2,13]. On the other hand, only a minority of patients who underwent PTCA (10/51) received an intravascular stent, which may reduce the need for repeated revascularization by as much as 50% [14]. Finally, our relative low intraoperative mortality agree with that showed in previous studies [2,15]. In the subgroup of patients selected on the basis of a significant amount of viable myocardium, this could have further contributed to the low in hospital event rate. If so, presence of viability should be evaluated before any decision about revascularization, particularly in high-risk patients. According to our results, the similarities in low hospital and follow-up mortality observed in PTCA patients as compared with CABG should be considered in the clinical management of those patients who have technical contraindication for CABG or decline the operation. 4.3. Study limitations This is a non-randomized study, but scheduled patients for revascularization were enrolled consecutively during a 3-year period. No data were available to further describe the two populations in terms of ischaemia beyond viability and data on regional wall motion was evaluated only at short-term.
Our results, despite the limited number of patients studied, fit a novel clinical decision making strategy in patients with left ventricular dysfunction and three-vessel disease. In these patients, PTCA of vessels perfusing viable myocardium, particularly the LAD, may represent an optimal choice in terms of short- and long-term survival, especially in patients with contraindications or higher risk for CABG. Moreover, the continuing progress in PTCA technology, and in the medical treatment of coronary atherosclerosis could offer in the near future new possibilities for improved non-surgical approaches to patients with ischaemic left ventricular dysfunction, multiple coronary vessel disease and viable myocardium. doi:10.1016/S1569-9293(03)00064-1
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Abstract
1. Introduction
