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Despite the success of medical therapy, percutaneous coronary interventions (PCIs), and coronary artery bypass grafting (CABG) in the treatment of coronary artery disease (CAD), there are a significant number of patients with refractory angina owing to diffuse CAD that is not amenable to PCI or CABG. This severe CAD can lead to incomplete revascularization and is noted to occur in up to 25% of CABG surgery.1 This incomplete revascularization is a powerful independent predictor of operative mortality and perioperative adverse events.1,2 Additionally, the presence of diseased but nongrafted arteries carries a poor prognosis and poses a significant negative influence leading to an increased incidence of death, recurrent angina, myocardial infarction (MI), and the need for repeat CABG.3,4

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Strategies to treat patients with end-stage coronary disease have sought to create or enhance myocardial angiogenesis. Such techniques include TMR as well as protein-, gene-, and cell-based therapies. TMR was founded, in part, on previous methods of providing direct perfusion to the myocardium. Prior attempts at direct perfusion were based on Wearn's description of sinusoids that allowed blood to flow directly from the ventricle into the myocardium.5 These arterioluminal connections provide perfusion in more primitive vertebrate hearts and occur clinically in children with pulmonary atresia, an intact ventricular septum, and proximal obstruction of the coronary arteries. Sen and colleagues6 used myocardial acupuncture to establish direct perfusion and theoretically to recreate a coronary microcirculation similar to that of the reptilian heart. Additional methods of attempting to improve myocardial blood flow include Beck's creation of a form of superficial angiogenesis as a response to epicardial and pericardial inflammation.7 Combining the acupuncture, implantation, and inflammation techniques, Boffi8 and Borst9 used hollow tubes implanted in the myocardium to establish direct perfusion. Results from all these procedures yielded limited success. The angina relief obtained was not long lasting, was difficult to replicate, and most important, eventually was overshadowed by the ability to perform CABG. The mechanical trauma that resulted in poor long-term patency of myocardial acupuncture was overcome in theory by using a laser to create the channels. Although Mirhoseini and colleagues10 and Okada and colleagues11 pioneered the use of a laser to perform this type of revascularization in conjunction with CABG in the early 1980s, the use of a laser as sole therapy to establish its efficacy required advancements in the technology. The carbon dioxide (CO2) laser used by Mirhoseini had a peak output of 80 W and, therefore, required a significant amount of time to complete a transmural channel. As a result, to perform TMR optimally, the heart had to be chilled and still. Increasing the output of the laser to 800 W allowed TMR to be performed on a beating heart. This breakthrough led to the widespread clinical application of TMR. Since then, more than 25,000 patients have been treated with TMR around the world, and results from individual institutions, multicenter studies, and ...

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