In 1996, physicians told Pat Gibbs, a 67-year-old cardiac patient from Alabama with severe angina, that nothing could be done for her. Refusing to give up, Gibbs underwent transmyocardial laser revascularization (TMR) therapy and today, lives pain-free. Some cardiologists say TMR’s benefit is merely a placebo effect, others say it is real. A growing market for the procedure, however, could muzzle the naysayers.
TMR is a surgical revascularization procedure that may be performed through either a minimally invasive or an open surgical approach. During the procedure, a cardiac surgeon utilizes a laser to create approximately 15 to 40 millimeter-sized channels through the myocardium to promote increased blood flow.
Experts have debated the mechanisms of relief and have dismissed the patent channel theory and the placebo effect as significant contributors. “The mechanism is likely multifactorial with denervation responsible for the acute benefits and angiogenesis responsible for the long-term benefits,” according to Allen et al (Anesthesiology Clin 2008;26:501–519).
The FDA in the late 1990s approved two TMR laser systems: the holmium:yttrium-aluminum-garnet (Ho:YAG) system (Cardiogenesis) and the CO2 Heart Laser (PLC Medical Systems). Gibbs was treated with the CO2 laser at the Washington Hospital Center in Washington, D.C., after she was rejected for a heart transplant because of her age.
In 2004, the Society of Thoracic Surgeons (STS) published guidelines that gave TMR a Class I/Level A recommendation as the sole therapy for patients with an ejection fraction greater than 30 percent and Class III or IV angina that is refractory to maximal medical therapy (Ann Thorac Surg 2004 Apr;77:1494-502). Five randomized trials showed a significant improvement in angina but none of the trials demostrated a significant survival benefit. In their 2008 analysis of the evidence, Allen et al cited a five-year follow-up that showed a significantly increased survival for patients randomized to Ho:YAG TMR compared with medical therapy (65 percent vs. 52 percent).
“It’s difficult to believe the placebo effect works for five years,” says Mark Tauscher, president and CEO of PLC Medical Systems.
The STS guidelines also support TMR as an adjunct to CABG, albeit with weaker evidence (Class IIa/Level B). Both TMR alone or in conjunction with CABG are reimbursable procedures. The guidelines do not consider percutaneous myocardial revascularization (PMR), which is not an approved technique in the U.S.
In 2005, Martin Leon, MD, and colleagues from Columbia University published results from a randomized, placebo-controlled trial with patients treated with a percutaneous approach they called direct myocardial revascularization (DMR). They concluded that treatment with DMR “provides no benefit beyond that of a similar sham procedure in patients blinded to their treatment.” But they went further to declare that the benefits from surgical TMR also could be attributed to a placebo effect (J Am Coll Cardiol 2005;46:1812-1819).
Keith A. Horvath, MD, director of the Cardiothoracic Research Program at the National Heart, Lung and Blood Institute, took Leon et al to task for extrapolating their findings from PMR to TMR. He wrote that at the time when Leon’s study was actually conducted (1999-2000), the PMR devices created a “3- to 4-mm endocardial laser divot” as opposed to the TMR devices, which create “channels through the full thickness of the myocardium.” Horvath also said that while the degree of pain relief might be subjective, objective imaging data show improved perfusion following TMR (J Am Coll Cardiol 2006;48:2354-55).
Leon responded, in the same issue of JACC, saying that he and his colleagues believed that their study “accurately highlights the potent placebo effects in this patient population. As such, this causes us to doubt the clinical benefits referenced in the surgical TMR literature.” He also said that most studies showed no quantitative perfusion improvements after surgical TMR and that even TMR plus CABG has no proven benefit over CABG alone. Leon did not respond to a request for a comment.
Allen et al cited several studies that used PET imaging and echocardiography to demonstrate an improved myocardial blood