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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Keith B. Allen Robert D. Dowling Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Allen, K. B. Articles by Shaar, C. J. Search for Related Content PubMed Articles by Allen, K. B. Articles by Shaar, C. J.

J Thorac Cardiovasc Surg 2001;121:601-603
© 2001 The American Association for Thoracic Surgery

Letters to the Editor

Reply

Department of Cardiothoracic Surgery Indiana Heart Institute at St Vincent Hospital and Health Care Center^a
Indianapolis, IN 46260
University of Louisville^b
Louisville, KY 40292

Reply to the Editor:

We read with interest the comments of Nathanson and Ihnken regarding the safety and efficacy of holmium transmyocardial revascularization (TMR) combined with coronary artery bypass grafting (CABG) in patients not amenable to complete revascularization by CABG alone. ¹ In that multicenter, prospective, randomized, single-blinded trial, patients who underwent CABG to graftable areas combined with TMR to areas that could not be grafted had reduced operative mortality (1.5% vs 7.6%; P = .02) compared with patients who underwent CABG alone. Furthermore, TMR/CABG patients also required less postoperative left ventricular support, experienced enhanced 30-day freedom from major adverse cardiac events (97% vs 91%; P = .04), and had improved 1-year survival according to Kaplan-Meier analysis (95% vs 89%; P = .05). Multivariable predictors of operative mortality in these demographically similar populations were CABG alone (odds ratio 5.3, confidence interval 1.1-25.7, P = .04) and increased age (odds ratio 1.1, confidence interval 1.0-1.2, P = .03).

In a similar prospective, randomized, multicenter trial using a carbon dioxide laser, Frazier and others ² reported results in 49 high-risk patients who would be incompletely revascularized by CABG alone. Similar to the results reported by Allen and colleagues, ¹ operative mortality was reduced after CABG/TMR when compared with CABG alone (9% vs 33%; P = .09).

At 1-year follow-up, CABG/TMR patients tended to have less class III/IV angina (P = .11), better angina class (P = .2), and fewer major adverse cardiac events (P = .09); however, differences between groups for these variables did not reach statistical significance. In a multivariable analysis at 1 year, however, the only predicator of death, myocardial infarction, or severe class III/IV angina was randomization to CABG alone (odds ratio 2.2, confidence interval 1.1-4.3, P = .03). Nathanson and Ihnken's lack of understanding of this finding is unclear to us. Although individual variables may not always reach significance, composites of those same "adverse events" analyzed by multivariable analysis may reach significance.

It is not clear why Nathanson and Ihnken refer to the difference in operative mortality observed in this study (and presumably the one by Frazier's group) as a "glaring disparity." As determined by Parsonnet risk modeling, the actual mortality rate in the control group was similar to the predicted mortality rate (7.6% vs 6.6%; P = .5). By contrast, the operative mortality rate after CABG/TMR tended to be less than the predicted rate (1.5% vs 6.3%; P = .06). Participants in this study were not ideal candidates for CABG because the diffuse nature of their coronary artery disease limited complete conventional revascularization. The 9% endarterectomy rate observed in these patients is evidence for the complexity required in their revascularization. The presence of diseased but nongrafted arteries poses a significant negative influence on event-free survival, defined as the absence of death, myocardial infarction, recurrent angina, and the need for repeat CABG. ³ Graham, Chambers, and Davies ⁴ concluded that diffuse distal coronary artery disease is a powerful independent predictor of operative mortality. Unfortunately, the presence of diffuse coronary artery disease is currently not included in commonly used models for predicting surgical risk.

A number of Nathanson and Ihnken's questions reflect a misunderstanding of our study design. Although patients could receive more than one graft to a major target area, at least one major target area could not be grafted; it was this area that was targeted for TMR. When TMR is performed as sole therapy, laser channels are typically distributed over the entire distal two thirds of the left ventricle. Although the evolving current practice when performing CABG/TMR is to also direct the laser to the entire left ventricle (or at least overlap grafted with ungraftable areas), this was not the case in this trial.

Early benefits observed after CABG/TMR must be analyzed in the context of potential study limitations, as pointed out in the original article. Although patients were blinded to their treatment, surgeons obviously knew how patients were randomized. Operative characteristics, therefore, could differ between groups, reflecting surgeon belief in TMR and an attempt to achieve as complete a revascularization as possible in the CABG-alone group. Operative characteristics, however, were similar between groups, including the number and distribution of arterial grafts, suggesting surgeon bias was not a factor.

Under ideal circumstances, a study should be done at one institution and by one investigator, a condition that limits variation. Practical limitations during clinical trials, however, necessitate some variation with appropriate statistical accounting. In this multicenter trial, conduct of the operation and postoperative care were center-specific but not different between groups at each center. Similarly, review of the distribution of randomization between centers demonstrated minimal disparity, and operative deaths were distributed randomly among centers.

In prospective randomized trials, patients with ischemic heart disease without conventional treatment options who received TMR as sole therapy had improvement in angina, better event-free survival, and reduction in cardiac-related rehospitalizations when compared with patients receiving medical therapy alone. ^5-7 Considering the increasing number of patients with diffuse coronary artery disease not amenable to complete revascularization by CABG alone, adjunctive TMR will likely play an increasingly beneficial role in patient care and warrants continued study.

12/8/112631

doi:10.1067/mtc.2001.112631

References

1. Allen KB, Dowling RD, DelRossi AJ, Realyvasques F, Lefrak EA, Pfeffer TA, et al. Transmyocardial laser revascularization combined with coronary artery bypass grafting: a multicenter, blinded, prospective, randomized, controlled trial. J Thorac Cardiovasc Surg 2000;119:540-9.[Abstract/Free Full Text]
   
2. Frazier OH, Boyce SW, Griffith BP, Hattler BG, Kadipassoglu KA, Lansing AM, et al. Transmyocardial revascularization using a synchronized CO₂ laser as a adjunct to coronary artery bypass grafting: results of a prospective, randomized, multi-center trial with 12-month follow-up. Circulation 1999;100(Suppl):I-248.
   
3. Schaff HV, Gersh BJ, Bluth JR, Danielson GK, Orszulak TA, Puga FJ, et al. Survival and functional status after coronary artery bypass grafting: results 10 to 12 years after surgery in 500 patients. Circulation 1983;68(Suppl):II-200-4.
   
4. Graham MM, Chambers RJ, Davies RF. Angiographic quantification of diffuse coronary artery disease: reliability and prognostic value for bypass operations. J Thorac Cardiovasc Surg 1999;118:618-27.[Abstract/Free Full Text]
   
5. Allen KB, Dowling RD, Fudge TL, Schoettle GP, Selinger SL, Deepak M, et al. Comparison of transmyocardial revascularization with medical therapy in patients with refractory angina. N Engl J Med 1999;341:1029-36.[Abstract/Free Full Text]
   
6. Frazier OH, March RJ, Horvath KA. Transmyocardial revascularization with a carbon dioxide laser in patients with end-stage coronary artery disease. N Engl J Med 1999;341:1021-8.[Abstract/Free Full Text]
   
7. Burkhoff D, Schmidt S, Schulman SP, Myers J, Resar J, Becker LC, et al. Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomized trial. Lancet 1999;354:885-90.[Medline]
   

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Keith B. Allen Robert D. Dowling Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Allen, K. B. Articles by Shaar, C. J. Search for Related Content PubMed Articles by Allen, K. B. Articles by Shaar, C. J.