Proposed mechanisms of action include stim- ulation of microcirculation, creation of myocardial scarring, and denervation of ischemic myocardium.922 Various energy sources have been used, including carbon dioxide XeCl excimer and holmium:YAG lasers.923 925 There is no con- vincing evidence that one energy source is superior to the others. TMR also has been combined with cardiac denerva- tion by thoracic sympathectomy.926 Numerous single-center and a few multicenter randomized trials have been published that compare TMR with medical therapy for relief of refractory angina.927 930 Most have shown better angina relief with TMR but no survival benefit. The exception is a single multicenter trial that shows a survival benefit as well as better relief of angina at 5 years.931 A 5-year follow-up of a multicenter, prospectively random- ized trial reported not only sustained angina relief but also improved survival in CCS Class IV angina, and patients with no additional options for therapy who were randomized to sole-therapy TMR.931 A meta-analysis of 7 RCTs involving 1053 patients evaluated the effect of TMR on survival and angina relief.932 The conclusion was that at 1 year, TMR improved angina class but not survival when used as the sole procedural intervention compared with medical therapy alone. A number of other series also have reported sustained angina relief and improved quality of life in randomized patients receiving TMR at 3 to 5 years after treatment (Section 5.10 for additional information on TMR in revascularization). A growing number of patients with SIHD have refractory angina, defined as multivessel CAD with ischemia and symptoms that cannot be controlled with medical therapy or surgical or percutaneous revascularization. 