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Ann Thorac Surg 2002;73:1888-1892
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

Factors influencing results and outcome after transmyocardial laser revascularization

^a Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany

Accepted for publication January 31, 2002.

* Address reprint requests to Dr Krabatsch, Department of Thoracic and Cardiovascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany
e-mail: krabatsch{at}dhzb.de

	Abstract

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Background. Transmyocardial laser revascularization (TMR) has been increasingly used during the recent past for patients with diffuse coronary artery disease. Because this operation is associated with significant morbidity and mortality, it is important to select patients for TMR who are likely to benefit from the procedure.

Methods. We performed an univariate logistic regression analysis of 20 factors on the benefits and outcomes of 134 patients who underwent isolated TMR at our institution between November 1994 and May 2000.

Results. Responders and nonresponders differed significantly with regard to the incidence of diabetes mellitus. For diabetic patients the chance of profiting from the TMR operation was only 43% of that of nondiabetic patients (odds ratio = 0.43 [0.20 to 0.92]). Furthermore, patients with a preoperative body mass index of less than 25 had a threefold increase in the probability of death during the first year after TMR as compared to patients whose body mass index was 25 or more (odds ratio = 2.97 [1.05 to 8.40]). The incidence of diabetes was also slightly but not significantly different between 1-year survivors and nonsurvivors.

Conclusions. In diabetic patients we recommend caution in selecting therapeutic TMR because outcomes are less satisfactory than in nondiabetics. Furthermore, patients with a body mass index below 25 have a significantly higher risk for death during the first postoperative year. Studies based on larger patient populations should follow.

	Introduction

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At present, the majority of patients who suffer from coronary artery disease can be sufficiently treated by percutaneous transluminal coronary angioplasty or bypass grafting. However, in some cases a diffuse disease with multiple stenoses reaching into the periphery of the vessels has developed for which these treatments offer only a limited chance of success.

Transmyocardial laser revascularization (TMR) has been used increasingly during the recent years in this patient population. The therapy is based on the creation of transmyocardial channels in the free wall of the left ventricle by means of a laser [1]. Several prospective, controlled, randomized studies were able to show that after TMR 70% of the patients operated on experienced a marked decline in angina symptoms and an increase in physical endurance and quality of life [2, 3]. Whereas the regional and global myocardial function seems not to be influenced by TMR, the question of an improvement in myocardial perfusion is still unanswered.

Originally it was assumed that after TMR, in analogy to the amphibian heart, oxygenated blood is directed from the left ventricular cavity into the intramyocardial vasculature. An increasing body of histologic evidence on early postoperative channel occlusion, however, has brought other theories with regard to the mechanism of action of TMR into the debate. Among these are speculation about a possible denervation of the heart by the laser [4] as well as a growing number of histologic findings that show increased neoangiogenesis in the areas surrounding the TMR channels [5, 6].

There is consensus that TMR is only indicated for patients who suffer from Canadian Cardiovascular Society class III or IV angina despite maximum medical therapy and who are not candidates for coronary artery bypass grafting, balloon angioplasty or heart transplantation.

About 25% to 30% of the patients who underwent TMR did not benefit from the procedure with regard to angina symptoms or physical endurance [2, 3]. Because TMR is associated with significant morbidity and mortality it would be valuable to assess preoperatively which patients will probably benefit from the procedure and which will not. Furthermore, it would be beneficial to know which patient group carries a relatively high risk for death within the first postoperative year. Therefore, we analyzed the factors influencing the benefits and outcomes of our group of TMR patients.

	Material and methods

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Patients
Within the period from November 1994 to May 2001 170 patients underwent sole TMR using the CO₂ Heart Laser (800 W; PLC Medical Systems, Milford, CT) at our institution. Among these patients, 149 were operated on before May 2000; therefore, they could have been followed up for at least 1 year. Fifteen of those did not undergo the complete 1-year follow-up investigations due to lack of compliance. The remaining 134 patients formed the basis of this study (90% follow-up). Routine follow-up investigations included physical examination, transesophageal echocardiography, physical stress test, and thallium perfusion scan; these tests were performed 3, 6, and 12 months postoperatively.

Indication for TMR
At our institution TMR is indicated when a patient who is not amenable to percutaneous transluminal coronary angioplasty or coronary artery bypass grafting because of severe diffuse coronary disease and suffers from CCS class III or IV angina despite maximum antianginal therapy (nitrates, ß-blockers, and angiotensin-converting enzyme inhibitors). Proof of viable but ischemic myocardium shown by echocardiography or the thallium perfusion test is required.

Operative technique
Patients were positioned in right lateral decubitus and an anterolateral thoracotomy in the fifth intercostal space was performed. After dissection of pleural adhesions from previous operations the pericardium was opened about 1 cm anterior to the phrenic nerve. All pericardial adhesions were dissected with special attention to open bypass grafts.

In all ischemic but vital regions of the left ventricle TMR was performed creating channels 1 cm apart using the CO₂ heart laser. Penetration of the entire ventricular wall was confirmed by transesophageal echocardiography. Laser pulse duration was adjusted to the wall thickness. After achieving hemostasis, two chest tubes were inserted and the chest closed.

Postoperative assessment
Whether a patient responded to the operation or not was decided by two physicians who were not involved in the treatment of the patient, based on the results of the 1-year follow-up investigation.

The CCS class was the major criterion. All patients whose condition improved by at least one class were considered responders (group R) and patients whose condition worsened were nonresponders (group non-R). Patients with unchanged angina symptoms were considered to be nonresponders unless they improved with regard to at least two minor criteria (Table 1).

To analyze factors that influence 1-year survival after TMR we compared all patients who died from cardiac causes during the first postoperative year (group non-S) with the remaining patients (group S).

Statistical analysis
For the two pairs of groups (R and non-R, S and non-S) we compared the 20 factors listed in Table 2. Mean value and 95% confidence intervals were calculated. We performed comparisons between two groups using the t test and Pearson’s ² test. The benefit and outcome factors were assessed by univariate logistic regression analysis. A p value less than 0.05 was considered significant.

	Results

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Benefit from TMR
Using the benefit criteria, after 1 year 84 patients were assessed as responders to TMR (62.7%, group R). Sixty-six patients improved by one or more CCS classes (49.3%) and 18 patients showed unchanged angina but were considered as responders due to improvement of two minor criteria (13.4%).

The group of nonresponders (n = 50) consisted of 32 patients with complete 1-year follow-up investigations and 18 patients who died during the first postoperative year from cardiac causes.

Five patients who died of noncardiac causes met the responder criteria at the time of the last available follow-up and therefore were assigned to group R. All preoperative data for groups R and non-R are given in Table 2.

The incidence of diabetes was the only significant difference between groups R and non-R. Diabetic patients had only a 43% chance of benefiting from the TMR operation (odds ratio = 0.43 [0.20 to 0.92] [Fig 1]).

View larger version (17K): [in this window] [in a new window]   Fig 1. Changes in Canadian Cardiovascular Society (CCS) class in the patients with and without diabetes. Mean and 95% confidence intervals are given. Bold lines indicate pre-transmyocardial laser revascularization (TMR) values; interrupted lines indicate values 1 year after TMR.

One-year survival after TMR
Group S consisted of 116 patients because 18 patients (group non-S) died of cardiac reasons during the first postoperative year. Five patients died for noncardiac reasons during the follow-up interval, resulting in an overall 1-year mortality of 17% and a cardiac-related 1-year mortality of 13.4%. All preoperative data for groups S and non-S are given in Table 3.

	Comment

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Only 63% of our patients benefited from TMR, which is a relatively low number. This may be the result of criteria of considering all patients who died from cardiac causes as nonresponders, even when some of them reported a significant decline in angina during previous follow-ups. However, we considered this algorithm more appropriate. From a practical point of view the procedure has failed when the patient died from cardiac causes during the first postoperative year. Of the 116 patients who underwent all 1-year follow-up tests 72% met the criteria for responding, which is comparable to the percentage found in other clinical TMR studies [2, 3, 7]. Unfortunately, the follow-up investigation of our study was complete in only 90% of the entire group, which somewhat limits the cogency of its results.

It was not necessary to perform a multivariate regression analysis because there was only one factor with significantly different incidence in the groups. The fact that diabetic patients with diffuse coronary artery disease benefit less often from TMR is a new. There could be indirect evidence for the critical role of angioneogenesis as a possible mechanism of action of TMR.

There are a number of factors that influence the intensity of arteriogenesis or angiogenesis in humans. In addition to the patient’s age [8, 9], different drugs [10–13], or hypercholestrolemia [14], diabetes is also known to decrease the amount of collateralization and neoangiogenesis [15, 16]. There is evidence for a different type of regulation of arteriogenesis and angiogenesis in diabetic patients compared to nondiabetics. On the one hand, there are processes with increased angiogenesis in diabetic patients, such as diabetic retinopathy. There are increased serum vascular endothelial growth factor-A levels in the diabetic patient. On the other hand, recent findings have documented reduced collateral formation in diabetics [16], which is probably a result of a decrease in reactivity of monocytes to vascular endothelial growth factor-A [15]. Because the release of nitric oxide plays a crucial role in vascular endothelial growth factor-induced angiogenesis [17], the known decrease in endothelial NO release in diabetics could be the reason for limited angiogenesis in diabetic patients [18].

It is a well-known fact that diabetic patients with coronary artery disease more often suffer from silent ischemia due to the existent diabetic neuropathy. It could be assumed, therefore, that diabetic patients who underwent TMR had less angina preoperatively. However, in our patient groups there were no significant differences with regard to the preoperative CCS class between diabetic and nondiabetic patients.

Tjomsland and colleagues [19] have already identified diabetes as a risk factor for increased morbidity and mortality after TMR. In our study, however, the difference of the incidence of diabetes in survivors and nonsurvivors missed the level of significance.

It has been known for many years that patients with coronary artery disease and lower BMI show a significantly worse long-term survival after coronary artery bypass grafting [20]. Schwann and associates [20] found in their analysis of more than 3,500 consecutive patients undergoing coronary artery bypass grafting that the group with a BMI less than 24 showed not only increased operative mortality but also impaired long-term survival. Therefore, it not surprising that in our TMR group these patients also had a worse survival rate. However, the concrete mechanism by which a low BMI leads to a higher mortality is still under debate and not fully understood.

In the future we will be more reluctant to use TMR in diabetic patients and those with a body mass index below 25. Whether these patients are less likely to profit from the TMR procedure should be confirmed by studies based on larger patient populations.

	Acknowledgments

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We are indebted to A. Gale for her assistance in preparing the manuscript and J. Stein for statistical calculations. We are grateful to E. Wenzel for meticulous collection of data.

	References

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