Ann Thorac Surg 2001;71:532-536
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
Survival after transmyocardial laser revascularization in relation to nonlasered perfused myocardial zones
Ernst-Guenter Kraatz, MDa,
Martin Misfeld, MDa,
Britta Jungbluth, MDa,
Hans-Hinrich Sievers, MDa
a Clinic of Cardiac Surgery, Medical University of Lübeck, Lübeck, Germany
Accepted for publication September 22, 2000.
Address reprint requests to Dr Sievers, Clinic of Cardiac Surgery, University Hospital of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
e-mail: sievers{at}medinf.mu-luebeck.de
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Abstract
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Background. Transmyocardial laser revascularization for severe diffuse coronary artery disease reduces angina significantly. The effect on survival, however, is questionable, and risk factors are not adequately addressed. Considering that transmyocardial laser revascularization channels do not remain patent for improving direct myocardial blood supply, other variables such as perfusion through open native or grafted vessels in remote non–transmyocardial laser revascularization areas are probably more important for survival. This hypothesis is the subject of the study.
Methods. Transmyocardial laser revascularization was performed with a CO2 laser system in 63 patients between October 1995 and December 1997. Patients received transmyocardial laser revascularization alone or in combination with coronary artery bypass grafting. The heart was divided into three perfusion zones as determined by the three major coronary arteries. Patients were divided into three groups according to the number of zones that were perfused by either a native coronary artery or a patent bypass graft: group 1 (n = 9), none; group 2 (n = 24), one; and group 3 (n = 30), two. Follow-up was performed at 3, 6, 12, 24, and 36 months and was 100% complete. Mean latest follow-up was 26.2 months, minimal follow-up of survivors was at least 12 months.
Results. Overall mortality was remarkably higher in group 1 (77.8%) compared with group 2 (20.8%, p = 0.005) and group 3 (13.3%, p = 0.001). Hospital mortality was 22.2% in group 1, 0% in group 2, and 3.3% in group 3. Late mortality was also higher in group 1 (55.5% versus 20.8%, and versus 9.9%, respectively). Cardiac deaths were more frequent in group 1 (55.5% versus 12.5% in group 2, p = 0.02, and versus 9.9% in group 3, p = 0.009). The number of perfused myocardial zones showed a significant influence for survival (p = 0.002).
Conclusions. These data give some directional evidence that survival seems to be beneficially affected by the number of nonlasered perfused myocardial zones through native vessels or grafts in patients undergoing transmyocardial laser revascularization.
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Introduction
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Since the early 1990s transmyocardial laser revascularization (TMLR) is a new method for treatment of coronary artery disease [1, 2]. There is a selected group of patients with severe coronary artery disease in whom conventional interventions like angioplasty or coronary artery bypass grafting (CABG) are not feasible. In these patients suffering therapy-refractory angina even under maximal anti-ischemic medication, TMLR has proven to be a valuable therapeutical option [3, 4]. Transmyocardial laser revascularization is also used for combined treatment when CABG alone is not able to achieve complete revascularization [5]. Previous studies investigating clinical outcome after TMLR have demonstrated significant improvement in angina [6]. Perioperative mortality has been reported to be in the range of 3% to 9.7%, and related factors are discussed controversially [7, 8]. Only scant information is available concerning intermediate-term survival after TMLR. Considering the fact that TMLR channels do not remain patent, there is an important question still not adequately addressed, whether survival after TMLR is related to TMLR alone or other factors such as open coronary arteries or grafts. Burkhoff and colleagues [9] reported that good blood flow to at least one region of the heart through a native artery or a patent vascular graft may reduce risk of perioperative and short-term mortality. This survival analysis was performed up to 12 months. The purpose of our study was to investigate the survival after TMLR in relation to the number of nonlasered perfused myocardial zones through native vessels or grafts in patients with midterm follow-up.
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Material and methods
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Transmyocardial laser revascularization was approved by the Ethical Committee of the University Hospital of Lübeck. All patients gave written informed consent to participate in the treatment. A total number of 63 patients who underwent TMLR or TMLR in combination with CABG between October 1995 and December 1997 were included in this study. Indication for TMLR was refractory angina despite maximal anti-ischemic medication or inability of complete myocardial revascularization with CABG or angioplasty. In all patients a myocardial thallium scintigraphy and cardioangiography was performed to assess ischemia and myocardial viability. Preoperative antianginal medication consisted of ß-blockers (48%), nitrates (86%), calcium-channel blockers (43%), and molsidomine (5%), which was continued postoperatively without major changes. Patients were followed-up at 3, 6, 12, 24, and 36 months.
Patient demographics
The mean age of the 63 patients who underwent TMLR was 67.8 ± 8.8 years. Thirty-five patients received TMLR therapy only and 28 patients TMLR with additional CABG. Nineteen patients (30%) were female. Forty-three patients had a history of myocardial infarction, among them 12 patients with a recent myocardial infarction within the last 90 days. Seventeen patients were diabetic. Eight patients had angioplasty, and 21 other patients had CABG previously. Mean left ventricular ejection fraction was 57% ± 15.2%. Mean preoperative risk score values according to the European System for Cardiac Operative Risk Evaluation (EuroSCORE) [10, 11] were not different among groups (Table 1).
Operative technique
For single TMLR a left anterolateral thoracotomy was performed through the fifth intercostal space. Transmyocardial laser revascularization in combination with CABG was performed through standard median sternotomy, and TMLR was performed after completing CABG and before weaning the patient off the heart-lung-machine. For TMLR an 800-W CO2 laser (PLC Medical Systems, Inc, Milford, MA) was used. Laser channels were placed in a density of approximately one channel/cm2. Energy applied was between 20 and 40 Joules. Spontaneous pulsatile bleeding from the laser channels and intraventricular vaporization bubbles detected by transesophageal echocardiography were considered as criteria for successful transmyocardial lasering.
Perioperative data
Perioperative data are shown in Table 2. The mean number of laser channels decreased in patients of groups 2 and 3 compared with patients with zero perfused myocardial zones (group 1).
Definition of perfused myocardial zones
Patients were divided into three groups with zero, one, and two perfused myocardial zones at TMLR. Therefore, the myocardium was divided into three zones anatomically corresponding to one of the main coronary arteries: right coronary artery, left anterior descending artery, and circumflex artery. Sufficient perfusion in these zones was assumed if there was a native vessel with less than 70% stenosis as estimated by preoperative angiogram or after CABG of one of the main coronary vessels (group 2: native vessel 20, bypass 4; group 3: native vessel only 6, bypass only 20, and native and bypass 4). Nine patients (group 1) had no perfused myocardial zones by this definition and underwent TMLR alone.
Statistical analysis
Survival rate was calculated by Kaplan-Meier analysis, and differences among groups were tested for significance with the log-rank test (SPSS for Windows Version 6.1, SPSS, Inc, Chicago, IL). A value of p less than 0.05 was considered to be statistically significant. For statistical analysis, relative frequencies were compared using 
2 test, Fisher’s exact test, and the Bonferroni correction. To test the effect of various variables on the probability of survival, logistic regression analysis was performed.
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Results
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Angina
Preoperatively, all patients had angina class Canadian Cardiovascular Society (CCS) III or more (Table 3). There was no patient lost to follow-up. Mean length of follow-up was 137.2 weeks (group 1), 127.6 weeks (group 2), and 121.7 weeks (group 3). At 12 months’ follow-up patients of all groups showed a significant improvement in angina class (Table 3). Angina class increased in 2 patients of group 1 at 36 months’ follow-up.
Mortality
Overall hospital mortality was 4.8%, and overall late mortality was 21%. In the group with zero perfused zones, 7 of 9 patients died within the follow-up period (77.8%). In the group with one perfused zone, 5 patients died (20.8%), whereas 4 patients (13.3%) with two perfused zones died (Table 4). Reasons for noncardiac deaths in 5 patients were end-stage renal failure, pulmonary embolism, stroke, mesenteric infarction, and cerebral hemorrhage. Figure 1 illustrates survival rate as a function of number of perfused myocardial zones. The incidence of cardiac-related deaths was also significantly higher in group1 compared with groups 2 and 3 (Table 4, group 1 versus group 2, p = 0.02; group 1 versus group 3, p = 0.009, Fisher’s exact test). After Bonferroni correction, group 1 versus group 2 just failed to reach statistical significance. We did not find a correlation between left ventricular ejection fraction and mortality nor did the risk stratification value differ significantly among the groups. Using logistic regression models for statistical analysis, various factors (sex, EuroSCORE, and diabetes) showed no significant evidence of an influence on survival in univariate models, whereas the body mass index (p = 0.035), the New York Heart Association score (p = 0.047), and the number of perfused myocardial zones (p = 0.002) were significantly associated with a greater chance of survival. In multivariate models, however, only the number of perfused myocardial zones remained statistically significant. When the presence or absence of additional CABG is included in the model, the ß-coefficient of the number of perfused myocardial zones was 2.5 (p < 0.001), and that associated with CABG was -2.2 (p = 0.041), suggesting that the number of perfused myocardial zones is most predictive (estimated odds ratio, 12.2) of survival and that the protection offered by a bypassed vessel is not as large as that offered by an open native vessel.
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Fig 1. Kaplan-Meier survival curves for patients with zero (group 1), one (group 2), or two (group 3) perfused myocardial zones.
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Comment
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This study provides some evidence that survival after TMLR seems to be dependent on the number of perfused myocardial zones, whereas improvement of angina at least in the first 12 months after the operation is less dependent on myocardial perfusion. Transmyocardial laser revascularization in patients with severe diffuse coronary artery disease with no option for conventional revascularization procedures has been reported to significantly improve angina [2–4, 6]. In our patients angina class was significantly decreased up to 36 months after TMLR, especially in patients with one or two perfused myocardial zones. However, in the only 2 surviving patients in group 1, angina increased between 24 and 36 months of follow-up, supporting the findings of Nägele and associates [6], who also observed an increase of angina after 12 months of follow-up. Survival was significantly improved if the myocardium was perfused through native or grafted vessels (group 2 and group 3). This was valid for hospital as well as late survival (Table 4). Hospital mortality of the 35 patients with TMLR only was 5.7%, comparing favorably with the 5% to 10% perioperative mortality reported in previous series [7, 8]. Overall mortality in the group with no perfused myocardial zone was 77.8%, whereas overall mortality in the group with one perfused myocardial zone was 20.8%, and with two perfused zones 13.3%. In addition, the Kaplan-Meier survival curve showed significant differences in survival of patients with perfused myocardial zones compared with patients with no perfused zones. A recent published study from Burkhoff and coworkers [9] demonstrated comparable results with a short-term follow-up to 1 year. Operative risk profile as judged by the EuroSCORE system was not different among groups, indicating no significant discriminant factor for survival. In addition, if left ventricular ejection fraction, as a determinant for early survival [7, 12, 13], was evaluated, we could not find a significant influence of this variable on hospital mortality, although 10 of our patients had a left ventricular ejection fraction between 25% and 40%. This may be related to the fact that we deliberately used the intraaortic balloon pump in patients with low left ventricular ejection fraction. There is also some evidence that increased body mass index and decreased New York Heart Association classification score are associated with greater chance of survival. However, the variable with smallest probability value is the number of perfused myocardial zones. There is very strong evidence of increased chance of survival with more perfused myocardial zones. Our statistical analysis also suggests, that although survival is improved by increased number of perfused myocardial zones, this effect is not nearly as strong when there has been an additional CABG performed. However, the probability value for CABG is only just less than 0.05, so not too much importance can be attached to this result.
Thus, perfusion of myocardial zones correlates well in our patients with overall and cardiac mortality after TMLR only or after TMLR in combination with CABG, indicating, indirectly, that TMLR only does not provide adequate improvement of myocardial perfusion. These findings underscore the reports of Burns and coworkers [14], who demonstrated no increase of myocardial perfusion after TMLR as judged by positron emission tomography scans, but is in contrast to the observation of Horvath and colleagues [3], who detected improved myocardial perfusion. Thus, the exact mechanism of TMLR remains speculative. Whether our findings support the theory that TMLR promotes some kind of blood distribution from the zone supplied by an open or grafted vessel into the remote lasered myocardial zone remains to be determined. Other possibilities have been proposed, including myocardial denervation, placebo effect, and angiogenesis [15–18]. In experimental animal studies, TMLR induced angiogenesis, and this fact may contribute to clinical benefit [16]. However, this mechanism cannot explain sufficiently the prompt relief of angina after the TMLR procedure, which occurs immediately thereafter. The theory of a psychological effect of TMLR is also questionable when patients show an improvement in angina class up to 36 months postoperatively in the groups with one and two perfused myocardial zones. Finally, unknown effects or the combination of the effects mentioned above cannot be excluded.
One limitation of the study is the fact that all patients underwent TMLR. There is neither a comparative group nor is this study a randomized trial. Furthermore, the number of patients in the different groups is rather small. Thus, multicenter prospective randomized trials are necessary. Nevertheless, our single-center study with a 100% follow-up was performed on the basis of homogeneous criteria for patient selection, operation, perioperative treatment, and reevaluation, providing directional data before forthcoming studies. Furthermore, we assumed that perfusion through open vessels or grafts provides adequate blood supply in the anatomically related zones (perfused myocardial zones). Nevertheless, it would be of benefit for the exact determination of myocardial perfusion to apply scintigraphic techniques or positron emission tomography scans.
In conclusion, our study provides some evidence that the number and having at least one perfused myocardial zone through native or grafted vessels seems to favorably influence postoperative survival. Although the exact mechanism of TMLR still remains uncertain, an additional blood supply (native vessel or graft) may be of a certain prognostic value. Therefore, we advocate all efforts to revascularize the myocardium at TMLR even if just a single graft is possible.
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Acknowledgments
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We thank PD Dr Hans-Jürgen Friedrich (Institute of Medical Biometry and Statistics, Medical University of Lübeck, Germany) and Dr Derek Robinson (Center for Statistics & Stochastic Modelling, School of Mathematical Sciences, University of Sussex, Brighton, UK) for their help in statistical analysis.
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Abstract
Introduction
