Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Transmyocardial revascularization was effective in refractory angina and left ventricular free-wall ischemia

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ACP J Club. 2000 May-June;132:85. doi:10.7326/ACPJC-2000-132-3-085

Related Content in this Issue
• Companion Abstract and Commentary: Transmyocardial revascularization increased exercise duration and reduced angina symptoms


Source Citation

Frazier OH, March RJ, Horvath KA, for the Transmyocardial Carbon Dioxide Laser Revascularization Study Group. Transmyocardial revascularization with a carbon dioxide laser in patients with end-stage coronary artery disease. N Engl J Med. 1999 Sep 30;341:1021-8. [PubMed ID: 10502591]


Abstract

Question

In patients with refractory angina and left ventricular free-wall ischemia that is not amenable to direct coronary revascularization, is transmyocardial revascularization (TMR) effective and safe for relieving angina?

Design

Randomized (allocation concealed*), blinded (outcome assessor),* controlled trial with 12-month follow-up.

Setting

12 centers in the United States.

Patients

192 patients (mean age 61 y, 79% men) who had class III or IV (Canadian Cardiovascular Society) angina that was refractory to medical treatment, reversible ischemia of the left ventricular free wall, and coronary disease that was not amenable to coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. Exclusion criteria were left ventricular ejection fraction < 20% or other major illness. Follow-up for relief of angina was 90% at 3 months, 81% at 6 months, and 73% at 12 months.

Intervention

Patients were allocated to TMR (n = 91) or medical treatment (n = 101). TMR was done by creating transmural channels (1 channel/cm2 of myocardial surface) approximately 1 mm in diameter with a single pulse of a carbon dioxide laser (peak power 850 W) through the left ventricle. 60 patients originally assigned to medical treatment crossed over to TMR because of unstable angina that required intravenous antianginal treatment for ≥ 48 hours in an intensive care unit.

Main outcome measures

Treatment success (reduction of ≥ 2 angina classes). Quality of life and cardiac perfusion were also evaluated in < 80% of surviving patients at 12 months.

Main results

TMR was better than medical treatment for relieving angina at 3 months (67% vs 20%, P < 0.001) and 6 months (67% vs 27%, P < 0.001).

Conclusion

In patients with refractory angina and left ventricular free-wall ischemia that is not amenable to direct coronary revascularization, transmyocardial revascularization was associated with an improvement in angina.

*See Glossary.

Source of funding: No external funding.

For correspondence: Dr. O.H. Frazier, Texas Heart Institute, P.O. Box 20345, Houston, TX 77225-0345, USA. FAX 713-794-6798.


Commentary

These 2 studies by Burkhoff and Frazier and their colleagues provide evidence that TMR may be beneficial for patients with severe angina for whom traditional revascularization is not an option. TMR is a surgical procedure done by creating laser holes in the left ventricular free wall via a thoracotomy in patients who are not candidates for coronary artery bypass grafting or percutaneous intervention. Although the mechanism for this benefit is not clear, the premise is that TMR stimulates angiogenesis and thereby improves myocardial perfusion (1). Another proposed theory is that TMR causes myocardial denervation, allowing for relief of symptoms (2). Support for either of these mechanisms in clinical practice is limited at present.

The Angina Treatments: Lasers and Normal Therapies in Comparison (ATLANTIC) study found that both exercise duration and angina scores improved significantly in the TMR group but not in the medically treated group. However, these investigators found no improvement in myocardial perfusion by thallium testing in either group. The placebo effect cannot be underestimated in this cohort of patients who had end-stage coronary artery disease and were eagerly seeking relief for their chest discomfort. This effect is shown in the recent VEGF [vascular endothelial growth factor] in Ischemia for Vascular Angiogenesis (VIVA) trial (3), a blinded trial of intravenous VEGF given to a similar patient population. As in the TMR trials, the treatment group in the VIVA trial substantially improved in angina class and exercise time, but the placebo group also showed a similar improvement. Although the ATLANTIC study shows symptomatic improvement using TMR, the benefit of a placebo effect has not been ruled out.

The trial by Frazier and colleagues also compared TMR with maximal medical therapy. They again found a significant improvement in angina class in the TMR group but not in the medically treated group. However, an improvement in ischemic regions on single-photon-emission-computed tomography was seen in the TMR but not in the medically treated group. A confounding issue in this study is that the trial design allowed for crossover from medical therapy to TMR if patients had refractory angina, and approximately 60% of the medically treated group received TMR. These crossover patients received a similar benefit to those primarily randomized to TMR.

The difficulty with assessing whether TMR truly improves symptoms is that operators feel that they cannot ethically perform sham thoracotomy operations. The recent advent of creating similar laser myocardial channels by percutaneous technique will better lend itself to double-blind trials. Until such randomized, double-blind, controlled trials are done, a placebo effect cannot be excluded.

Brigitta C. Brott, MD
The Heart Group
Evansville, Indiana, USA


References

1. Yamamoto N, Kohmoto T, Gu A, et al. Angiogenesis is enhanced in ischemic canine myocardium by transmyocardial laser revascularization. J Am Coll Cardiol. 1998;31:1426-33.

2. Hirsch GM, Thompson GW, Arora RC, et al. Transmyocardial laser revascularization does not denervate the canine heart. Ann Thorac Surg. 1999;68:460-8.

3. Henry TD, Annex BH, Axrin MA, et al. Double blind, placebo controlled trial of recombinant human vascular endothelial growth factor—the VIVA trial [Abstract]. J Am Coll Cardiol. 1999;33:384A.